To see the other types of publications on this topic, follow the link: Cancer cells Breast Genes.
Journal articles on the topic 'Cancer cells Breast Genes'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Cancer cells Breast Genes.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Dai, Xiaofeng, Rong Ma, Xijiang Zhao, and Fengfeng Zhou. "Epigenetic profiles capturing breast cancer stemness for triple negative breast cancer control." Epigenomics 11, no. 16 (December 2019): 1811–25. http://dx.doi.org/10.2217/epi-2019-0266.
Full textAbstract:
Aim: Triple-negative breast cancers (TNBCs) contain a higher percentage of breast cancer stem cells (BCSCs) than the other subtypes and lack effective yet safe-targeted therapies. We would like to unveil genes relevant to the therapeutic control of breast cancer stemness at the epigenetic level. Methods: We sequenced the transcriptome of BCSCs isolated from TNBCs, identified genes differentially expressed in these cells and subjected to DNA methylation and established the Bayesian network as well as interactions out of them. Results & conclusion: We presented a core epigenetic BCSC gene panel consisting of eight genes that can be used for BCSCs and TNBCs identification, and revealed the dominant roles of FOXA1 and GATA3 in orchestrating breast cancer heterogeneity and stemness.
2
Liu, Li, Yudong Wu, Cheng Zhang, Chong Zhou, Yining Li, Yi Zeng, Chunbo Zhang, et al. "Cancer-associated adipocyte-derived G-CSF promotes breast cancer malignancy via Stat3 signaling." Journal of Molecular Cell Biology 12, no. 9 (April 2, 2020): 723–37. http://dx.doi.org/10.1093/jmcb/mjaa016.
Full textAbstract:
Abstract Adipocyte is the most predominant cell type in the tumor microenvironment of breast cancer and plays a pivotal role in cancer progression, yet the underlying mechanisms and functional mediators remain elusive. We isolated primary preadipocytes from mammary fat pads of human breast cancer patients and generated mature adipocytes and cancer-associated adipocytes (CAAs) in vitro. The CAAs exhibited significantly different gene expression profiles as assessed by transcriptome sequencing. One of the highly expressed genes in CAAs is granulocyte colony-stimulating factor (G-CSF). Treatment with recombinant human G-CSF protein or stable expression of human G-CSF in triple-negative breast cancer (TNBC) cell lines enhanced epithelial–mesenchymal transition, migration, and invasion of cancer cells, by activating Stat3. Accordantly, targeting G-CSF/Stat3 signaling with G-CSF-neutralizing antibody, a chemical inhibitor, or siRNAs for Stat3 could all abrogate CAA- or G-CSF-induced migration and invasion of breast cancer cells. The pro-invasive genes MMP2 and MMP9 were identified as target genes of G-CSF in TNBC cells. Furthermore, in human breast cancer tissues, elevated G-CSF expression in adipocytes is well correlated with activated Stat3 signal in cancer cells. Together, our results suggest a novel strategy to intervene with invasive breast cancers by targeting CAA-derived G-CSF.
3
Hwang-Verslues, Wendy W., King-Jen Chang, Eva Y. H. P. Lee, and Wen-Hwa Lee. "Breast Cancer Stem Cells and Tumor Suppressor Genes." Journal of the Formosan Medical Association 107, no. 10 (October 2008): 751–66. http://dx.doi.org/10.1016/s0929-6646(08)60188-6.
Full text
4
Kim, Young-Ho, Hyun-Kyoung Kim, Hee Yeon Kim, HyeRan Gawk, Seung-Hyun Bae, Hye Won Sim, Eun-Kyung Kang, Ju-Young Seoh, Hyonchol Jang, and Kyeong-Man Hong. "FAK-Copy-Gain Is a Predictive Marker for Sensitivity to FAK Inhibition in Breast Cancer." Cancers 11, no. 9 (September 2, 2019): 1288. http://dx.doi.org/10.3390/cancers11091288.
Full textAbstract:
Background: Cancers with copy-gain drug-target genes are excellent candidates for targeted therapy. In order to search for new predictive marker genes, we investigated the correlation between sensitivity to targeted drugs and the copy gain of candidate target genes in NCI-60 cells. Methods: For eight candidate genes showing copy gains in NCI-60 cells identified in our previous study, sensitivity to corresponding target drugs was tested on cells showing copy gains of the candidate genes. Results: Breast cancer cells with Focal Adhesion Kinase (FAK)-copy-gain showed a significantly higher sensitivity to the target inhibitor, FAK inhibitor 14 (F14). In addition, treatment of F14 or FAK-knockdown showed a specific apoptotic effect only in breast cancer cells showing FAK-copy-gain. Expression-profiling analyses on inducible FAK shRNA-transfected cells showed that FAK/AKT signaling might be important to the apoptotic effect by target inhibition. An animal experiment employing a mouse xenograft model also showed a significant growth-inhibitory effect of F14 on breast cancer cells showing FAK-copy-gain, but not on those without FAK-copy-gain. Conclusion: FAK-copy-gain may be a predictive marker for FAK inhibition therapy in breast cancer.
5
Bogacz, Anna, Marlena Wolek, Bogna Juskowiak, Monika Karasiewicz, Adam Kamiński, Izabela Uzar, Anna Polaszewska, Zofia Kostrzewa, and Bogusław Czerny. "Expression of genes modulated by epigallocatechin-3-gallate in breast cancer cells." Herba Polonica 64, no. 3 (September 1, 2018): 31–37. http://dx.doi.org/10.2478/hepo-2018-0016.
Full textAbstract:
Summary Introduction: Breast cancer is the most common malignant cancer among women. Both drug resistance and metastasis are major problems in the treatment of breast cancer. Therefore, adjuvant therapy may improve patients’ survival and affect their quality of life. It is suggested that epigallocatechin gallate (EGCG) which is well known for its chemopreventive activity and acts on numerous molecular targets may inhibit the growth and metastasis of some cancers. Hence, discovering the metastatic molecular mechanisms for breast cancer may be useful for therapy. Objective: The aim of the study was to determine the effect of EGGC on the mRNA expression level of genes such as ZEB1, ABCB1, MDM2, TWIST1 and PTEN in MCF-7 breast cancer cells. Methods: MCF7/DOX were cultured in the presence of 0.2 μM DOX and EGCG (20-50 μM). The mRNA expression level was determined by real-time quantitative PCR using RealTime ready Custom Panel 96 kit. Results: Our results showed an important increase (about 2-fold for 20 μM EGCG + 0.2 μM DOX and 2.5-fold for 50 μM EGCG + 0.2 μM DOX, p<0.05) in ZEB1 expression levels. In case of ABCB1 gene lack of influence on the mRNA level was observed (p>0.05). We also observed significant decrease of ZEB1 expression in MCF7 cells with 20 μM and 50 μM EGCG (p<0.05). In addition, EGCG (20 μM) caused an increase of MDM2 and PTEN mRNA levels in almost 100% (p<0.05) and 40% (p>0.05), respectively. Lack of the influence of EGCG was noted for the TWIST1 gene expression. In case of MCF7/DOX we showed an increase of mRNA level of PTEN gene about 50% (p<0.05). Conclusions: These results suggest that EGCG may be potentially used in adjuvant therapy in the breast cancer treatment.
6
Zhang, Suping, Han Zhang, Emanuela M. Ghia, Jiajia Huang, Liufeng Wu, Jianchao Zhang, Sharon Lam, et al. "Inhibition of chemotherapy resistant breast cancer stem cells by a ROR1 specific antibody." Proceedings of the National Academy of Sciences 116, no. 4 (January 8, 2019): 1370–77. http://dx.doi.org/10.1073/pnas.1816262116.
Full textAbstract:
Breast cancers enduring treatment with chemotherapy may be enriched for cancer stem cells or tumor-initiating cells, which have an enhanced capacity for self-renewal, tumor initiation, and/or metastasis. Breast cancer cells that express the type I tyrosine kinaselike orphan receptor ROR1 also may have such features. Here we find that the expression of ROR1 increased in breast cancer cells following treatment with chemotherapy, which also enhanced expression of genes induced by the activation of Rho-GTPases, Hippo-YAP/TAZ, or B lymphoma Mo-MLV insertion region 1 homolog (BMI1). Expression of ROR1 also enhanced the capacity of breast cancer cells to invade Matrigel, form spheroids, engraft in Rag2−/−γc−/− mice, or survive treatment with paclitaxel. Treatment of mice bearing breast cancer patient-derived xenografts (PDXs) with the humanized anti-ROR1 monoclonal antibody cirmtuzumab repressed expression of genes associated with breast cancer stemness, reduced activation of Rho-GTPases, Hippo-YAP/TAZ, or BMI1, and impaired the capacity of breast cancer PDXs to metastasize or reengraft Rag2−/−γc−/− mice. Finally, treatment of PDX-bearing mice with cirmtuzumab and paclitaxel was more effective than treatment with either alone in eradicating breast cancer PDXs. These results indicate that targeting ROR1 may improve the response to chemotherapy of patients with breast cancer.
7
Neiger, Hannah E., Emily L. Siegler, and Yihui Shi. "Breast Cancer Predisposition Genes and Synthetic Lethality." International Journal of Molecular Sciences 22, no. 11 (May 25, 2021): 5614. http://dx.doi.org/10.3390/ijms22115614.
Full textAbstract:
BRCA1 and BRCA2 are tumor suppressor genes with pivotal roles in the development of breast and ovarian cancers. These genes are essential for DNA double-strand break repair via homologous recombination (HR), which is a virtually error-free DNA repair mechanism. Following BRCA1 or BRCA2 mutations, HR is compromised, forcing cells to adopt alternative error-prone repair pathways that often result in tumorigenesis. Synthetic lethality refers to cell death caused by simultaneous perturbations of two genes while change of any one of them alone is nonlethal. Therefore, synthetic lethality can be instrumental in identifying new therapeutic targets for BRCA1/2 mutations. PARP is an established synthetic lethal partner of the BRCA genes. Its role is imperative in the single-strand break DNA repair system. Recently, Olaparib (a PARP inhibitor) was approved for treatment of BRCA1/2 breast and ovarian cancer as the first successful synthetic lethality-based therapy, showing considerable success in the development of effective targeted cancer therapeutics. Nevertheless, the possibility of drug resistance to targeted cancer therapy based on synthetic lethality necessitates the development of additional therapeutic options. This literature review addresses cancer predisposition genes, including BRCA1, BRCA2, and PALB2, synthetic lethality in the context of DNA repair machinery, as well as available treatment options.
8
R., Abhirup H., Priyanka Kenchetty, and Aishwarya K. Chidananda. "Breast ovarian cancer syndrome." International Surgery Journal 8, no. 8 (July 28, 2021): 2454. http://dx.doi.org/10.18203/2349-2902.isj20213144.
Full textAbstract:
BRCA1 and BRCA2, known as breast and ovarian cancer predisposition genes, were discovered in the 1990s. As part of a normal genetic structure, these genes are intrinsic to all human beings, but they are mutated in some individuals increasing the risk for breast and ovarian cancers development. BRCA1 is not only expressed in endocrine tissues but is also detected in other cells such as the neuroepithelial cells in the early stage of cell development. Like BRCA1, BRCA2 is also expressed in a wide variety of tissues and is observed with higher rates in the breast and thymus and with lower rates in the lung, ovary and spleen. We presented to you a case of 40 year old female admitted in surgical ward with lump in the left breast since 2 months with ipsilateral discrete axillary lymphadenopathy. Bilateral sono-mammography showed BIRADS V lesion in left breasts with satellite nodules. Ultrasonography of abdomen and pelvis showed large left adnexal solid mass lesion and right sided ovarian cyst with retrocaval, preaortic lymphadenopathy. Patient underwent a diagnostic laparoscopy which was converted to a laparotomy. Total abdominal hysterectomy with bilateral salphingo-oophorectomy was done. For the breast lump, patient underwent left sided modified radical mastectomy. Gene testing for revealed BRCA1 positivity. Chemotherapy was given to cover both breast and ovarian carcinoma. Patient came back with abdominal distension after 9 months and was offered palliative care. Patient succumbed for disease after 1 year after diagnosis. We reviewed the literature for the same.
9
Rossi, Fabiana Alejandra, Ezequiel Hernán Calvo Roitberg, Juliana Haydeé Enriqué Steinberg, Molishree Umesh Joshi, Joaquín Maximiliano Espinosa, and Mario Rossi. "HERC1 Regulates Breast Cancer Cells Migration and Invasion." Cancers 13, no. 6 (March 15, 2021): 1309. http://dx.doi.org/10.3390/cancers13061309.
Full textAbstract:
Tumor cell migration and invasion into adjacent tissues is one of the hallmarks of cancer and the first step towards secondary tumors formation, which represents the leading cause of cancer-related deaths. This process is considered an unmet clinical need in the treatment of this disease, particularly in breast cancers characterized by high aggressiveness and metastatic potential. To identify and characterize genes with novel functions as regulators of tumor cell migration and invasion, we performed a genetic loss-of-function screen using a shRNA library directed against the Ubiquitin Proteasome System (UPS) in a highly invasive breast cancer derived cell line. Among the candidates, we validated HERC1 as a gene regulating cell migration and invasion. Furthermore, using animal models, our results indicate that HERC1 silencing affects primary tumor growth and lung colonization. Finally, we conducted an in silico analysis using publicly available protein expression data and observed an inverse correlation between HERC1 expression levels and breast cancer patients’ overall survival. Altogether, our findings demonstrate that HERC1 might represent a novel therapeutic target for the development or improvement of breast cancer treatment.
10
Wijshake, Tobias, Zhongju Zou, Beibei Chen, Lin Zhong, Guanghua Xiao, Yang Xie, John G. Doench, Lynda Bennett, and Beth Levine. "Tumor-suppressor function of Beclin 1 in breast cancer cells requires E-cadherin." Proceedings of the National Academy of Sciences 118, no. 5 (January 25, 2021): e2020478118. http://dx.doi.org/10.1073/pnas.2020478118.
Full textAbstract:
Beclin 1, an autophagy and haploinsufficient tumor-suppressor protein, is frequently monoallelically deleted in breast and ovarian cancers. However, the precise mechanisms by which Beclin 1 inhibits tumor growth remain largely unknown. To address this question, we performed a genome-wide CRISPR/Cas9 screen in MCF7 breast cancer cells to identify genes whose loss of function reverse Beclin 1-dependent inhibition of cellular proliferation. Small guide RNAs targeting CDH1 and CTNNA1, tumor-suppressor genes that encode cadherin/catenin complex members E-cadherin and alpha-catenin, respectively, were highly enriched in the screen. CRISPR/Cas9-mediated knockout of CDH1 or CTNNA1 reversed Beclin 1-dependent suppression of breast cancer cell proliferation and anchorage-independent growth. Moreover, deletion of CDH1 or CTNNA1 inhibited the tumor-suppressor effects of Beclin 1 in breast cancer xenografts. Enforced Beclin 1 expression in MCF7 cells and tumor xenografts increased cell surface localization of E-cadherin and decreased expression of mesenchymal markers and beta-catenin/Wnt target genes. Furthermore, CRISPR/Cas9-mediated knockout of BECN1 and the autophagy class III phosphatidylinositol kinase complex 2 (PI3KC3-C2) gene, UVRAG, but not PI3KC3-C1–specific ATG14 or other autophagy genes ATG13, ATG5, or ATG7, resulted in decreased E-cadherin plasma membrane and increased cytoplasmic E-cadherin localization. Taken together, these data reveal previously unrecognized cooperation between Beclin 1 and E-cadherin–mediated tumor suppression in breast cancer cells.
11
Liu, Yan, Ai Zhang, Ping-Ping Bao, Li Lin, Yina Wang, Haijian Wu, Xiao-Ou Shu, Aiguo Liu, and Qiuyin Cai. "MicroRNA-374b inhibits breast cancer progression through regulating CCND1 and TGFA genes." Carcinogenesis 42, no. 4 (January 22, 2021): 528–36. http://dx.doi.org/10.1093/carcin/bgab005.
Full textAbstract:
Abstract Emerging evidence indicates that microRNAs (miRNAs) play a critical role in breast cancer development. We recently reported that a higher expression of miR-374b in tumor tissues was associated with a better disease-free survival of triple-negative breast cancer (TNBC). However, the functional significance and molecular mechanisms underlying the role of miR-374b in breast cancer are largely unknown. In this current study, we evaluated the biological functions and potential mechanisms of miR-374b in both TNBC and non-TNBC. We found that miR-374b was significantly downregulated in breast cancer tissues, compared to adjacent tissues. MiR-374b levels were also lower in breast cancer cell lines, as compared to breast epithelial cells. In vitro and in vivo studies demonstrated that miR-374b modulates the malignant behavior of breast cancer cells, such as cell proliferation in 2D and 3D, cell invasion ability, colony-forming ability and tumor growth in mice. By using bioinformatics tools, we predicted that miR-374b plays a role in breast cancer cells through negatively regulating cyclin D1 (CCND1) and transforming growth factor alpha (TGFA). We further confirmed that CCND1 and TGFA contribute to the malignant behavior of breast cancer cells in vitro and in vivo. Our rescue experiments showed that overexpressing CCND1 or TGFA reverses the phenotypes caused by miR-374b overexpression. Taken together, our studies suggest that miR-374b modulates malignant behavior of breast cancer cells by negatively regulating CCND1 and TGFA genes. The newly identified miR-374b-mediated CCND1 and TGFA gene silencing may facilitate a better understanding of the molecular mechanisms of breast cancer progression.
12
Gerashchenko, Tatiana S., Sofia Y. Zolotaryova, Artem M. Kiselev, Liubov A. Tashireva, Nikita M. Novikov, Nadezhda V. Krakhmal, Nadezhda V. Cherdyntseva, Marina V. Zavyalova, Vladimir M. Perelmuter, and Evgeny V. Denisov. "The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer." Cancers 12, no. 7 (July 15, 2020): 1909. http://dx.doi.org/10.3390/cancers12071909.
Full textAbstract:
Intratumor morphological heterogeneity reflects patterns of invasive growth and is an indicator of the metastatic potential of breast cancer. In this study, we used this heterogeneity to identify molecules associated with breast cancer invasion and metastasis. The gene expression microarray data were used to identify genes differentially expressed between solid, trabecular, and other morphological arrangements of tumor cells. Immunohistochemistry was applied to evaluate the association of the selected proteins with metastasis. RNA-sequencing was performed to analyze the molecular makeup of metastatic tumor cells. High frequency of metastases and decreased metastasis-free survival were detected in patients either with positive expression of KIF14 or Mieap or negative expression of EZR at the tips of the torpedo-like structures in breast cancers. KIF14- and Mieap-positive and EZR-negative cells were mainly detected in the torpedo-like structures of the same breast tumors; however, their transcriptomic features differed. KIF14-positive cells showed a significant upregulation of genes involved in ether lipid metabolism. Mieap-positive cells were enriched in genes involved in mitophagy. EZR-negative cells displayed upregulated genes associated with phagocytosis and the chemokine-mediated signaling pathway. In conclusion, the positive expression of KIF14 and Mieap and negative expression of EZR at the tips of the torpedo-like structures are associated with breast cancer metastasis.
13
Shihab, Israa, Bariaa A. Khalil, Noha Mousaad Elemam, Ibrahim Y. Hachim, Mahmood Yaseen Hachim, Rifat A. Hamoudi, and Azzam A. Maghazachi. "Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment." Cancers 12, no. 8 (August 9, 2020): 2226. http://dx.doi.org/10.3390/cancers12082226.
Full textAbstract:
The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer. These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified. In this review, we discuss the activities of certain genes involved in the cross-talk among NK cells and breast cancer. Consequently, altering tumor immune microenvironment can make breast tumors more responsive to immunotherapy.
14
Wang, Shuning, Xiaoju Li, Wangqian Zhang, Yuan Gao, Kuo Zhang, Qiang Hao, Weina Li, et al. "Genome-Wide Investigation of Genes Regulated by ERα in Breast Cancer Cells." Molecules 23, no. 10 (October 5, 2018): 2543. http://dx.doi.org/10.3390/molecules23102543.
Full textAbstract:
Estrogen receptor alpha (ERα), which has been detected in over 70% of breast cancer cases, is a driving factor for breast cancer growth. For investigating the underlying genes and networks regulated by ERα in breast cancer, RNA-seq was performed between ERα transgenic MDA-MB-231 cells and wild type MDA-MB-231 cells. A total of 267 differentially expressed genes (DEGs) were identified. Then bioinformatics analyses were performed to illustrate the mechanism of ERα. Besides, by comparison of RNA-seq data obtained from MDA-MB-231 cells and microarray dataset obtained from estrogen (E2) stimulated MCF-7 cells, an overlap of 126 DEGs was screened. The expression level of ERα was negatively associated with metastasis and EMT in breast cancer. We further verified that ERα might inhibit metastasis by regulating of VCL and TNFRSF12A, and suppress EMT by the regulating of JUNB and ID3. And the relationship between ERα and these genes were validated by RT-PCR and correlation analysis based on TCGA database. By PPI network analysis, we identified TOP5 hub genes, FOS, SP1, CDKN1A, CALCR and JUNB, which were involved in cell proliferation and invasion. Taken together, the whole-genome insights carried in this work can help fully understanding biological roles of ERα in breast cancer.
15
JOSEPH JERRY, D., NICHOLAS B. GRINER, and LUWEI TAO. "TUMOR SUPPRESSOR PATHWAYS AND CELLULAR ORIGINS OF BREAST CANCER: NEW COMPLEXITIES AND NEW HOPES." Nano LIFE 01, no. 01n02 (March 2010): 1–16. http://dx.doi.org/10.1142/s179398441000002x.
Full textAbstract:
Heritable breast cancer syndromes have identified the recognition and processing of DNA double strand breaks as a fundamental vulnerability in the breast epithelium. The role of homology-directed DNA repair is particularly prominent, indicating that this repair pathway is rate-limiting. Although the activities of the tumor suppressor genes underlying heritable breast cancer act in a common pathway of DNA double strand break repair, the specific lesions result in surprisingly different patterns of biomarkers in the breast cancers, suggesting that they arise from different cell types that include the luminal, basal and progenitor cells within the breast epithelium. Therefore, each cell type appears to have distinct underlying vulnerabilities in repair of DNA double strand breaks. While the heterogeneity of targets poses a challenge to develop specific therapies, these pathways also render tumor cells sensitive to drugs targeting double strand break repair pathways offering new options for therapies. As double strand break repair is a common pathway underlying breast cancer risk, therapies that enhance the proficiency of this pathway offer a strategy for chemoprevention.
16
Sharma, D., B. B. Knight, R. Yacoub, T. Liu, L. Taliaferro-Smith, A. Nagalingam, and R. M. O'Regan. "Using epigenetic reprogramming to target triple-negative breast cancer." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e14565-e14565. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e14565.
Full textAbstract:
e14565 Background: The outcome for patients with breast cancer has been significantly improved by the use of targeted agents. The prognosis of triple negative (TN) breast cancers, which do not express hormone receptors (ER, PR) or Her2, is poor, because of an aggressive clinical course and lack of targeted therapeutic agents. Epigenetic silencing of specific genes has been observed in breast cancer and some of these genes are more important due to available targeted therapies such as ER. Since all endocrine therapies are designed to block ER function in some way, the identification of new therapies or strategies that could sensitize TN breast cancers to existing endocrine therapy could provide a revolutionary means of treating this aggressive subtype of cancer Methods: We examined the efficacy of combined treatment of HDAC inhibitor LBH589 and DNMT inhibitor decitabine to regenerate ER and PR in TN breast cancer cells using RT-PCR and immunoblotting. Changes in growth and proliferation of TN breast cancer cells in response to LBH589 and decitabine treatment were determined by XTT, BrdU incorporation and colony formation assay. Changes in apoptotic proteins were determined by western blotting. Athymic nude mice were used to establish pre-clinical models for TN breast cancer cells and effectiveness of combined treatment of LBH589 and decitabine was determined. Tumors biopsies were analyzed for ER and PR re-expression by western blot analysis and immunohistochemistry at the end of the treatment. Results: Combined treatment of LBH589 and decitabine resulted in re-expression of ER and PR in TN breast cancers in vitro and in vivo. Although re-expression of ER and PR were noted following LBH589 treatment alone, re-expression was more robust with the combination. TN breast cancer cells showing re-expressed ER can be targeted with tamoxifen. Tamoxifen inhibits growth of TN breast cancer cells re- expressing ER by triggering apoptosis. Conclusions: The importance of epigenetic events such as DNA methylation and HDAC inhibition in tumor progression is becoming increasingly evident. A trial evaluating the ability of LBH589 and decitabine to re- express ER, which can then be targeted by tamoxifen, is planned in patients with metastatic TN breast cancer. No significant financial relationships to disclose.
17
Karami, Faezeh, Narges Maleki, Arefeh Khazraei Monfared, and Sayeh Jafari Marandi. "Upregulation of miR-206 is a potential diagnostic biomarker in breast cancer." Bionatura 6, no. 2 (May 15, 2021): 1757–62. http://dx.doi.org/10.21931/rb/2021.06.02.15.
Full textAbstract:
Breast cancer is one of the most common malignancies, and like most cancers, most cases are caused by somatic mutations. Due to estrogen's role in the growth, differentiation, and division of breast and endometrial cancer cells, tamoxifen is used as an estrogen receptor antagonist in breast cancer cells with estrogen receptor (ER +) has a special place, which unfortunately in one-third of the Cases are resisted. This study aimed to investigate the effect of tamoxifen-treated tumor-derived exosomes on the expression pattern of Twist and Bcl-2 oncogenic genes in fibroblast cells. MCF-7 breast cancer cell line and fibroblast cells were purchased and cultured in a complete culture medium. After the appropriate number of cells was reached, they were treated with the appropriate concentration of tamoxifen. Cellular supernatant was then gathered in flasks, and exosomes were extracted from them. After extracting RNA from exosomes and cDNA synthesis, the expression level of miR-206, Twist-1, and Bcl-2 genes were evaluated using the Real-Time PCR method. The electronic microscope results confirmed the correctness of the exosomes isolated from the tumor cell culture medium. It has also been shown that tamoxifen treatment increases the expression of miR-206 in exosomes derived from breast tumor cells. The control group which has been kept untreated induced the expression level of Twist-1 and Bcl-2 genes time-dependently. However, when tamoxifen-treated tumor-derived exosomes treated the target cells, the expression level of oncogenic miRs Twist-1 and Bcl-2 were declined over time. Overall, this study showed that tamoxifen treatment on breast cancer cells could apply its antioncogenic effects on tumor stromal cells, such as fibroblasts, by altering the expression levels of exosomal microRNAs in tumor cells.
18
Kocemba-Pilarczyk, Kinga A., Paulina Dudzik, and Katarzyna Leśkiewicz. "The relationship between expression of VIMENTIN and CD146 genes in breast cancer." Bio-Algorithms and Med-Systems 17, no. 1 (March 1, 2021): 1–7. http://dx.doi.org/10.1515/bams-2020-0058.
Full textAbstract:
Abstract Objectives CD146 is an adhesive molecule that was originally reported on malignant melanoma cells as a protein crucial for cell adhesion. It is now known that high expression of the CD146 protein is not only characteristic of melanoma, but it occurs on a number of cancers, contributing to worse prognosis and increased aggressiveness. Independent in vitro studies in breast cancer have shown that CD146 protein alone can induce a change in epithelial to mesenchymal transcriptional profile, which is the basis of the tumor aggressiveness and metastasis. Methods In the following work, the correlation coefficients were analyzed between the genes of the mesenchymal profile and the CD146 gene in 10 independent transcriptomic data of breast cancer patients. Results The analysis confirmed the relationship between CD146 expression and mesenchymal profile genes, pointing VIMENTIN as the gene which expression is most strongly correlated with the CD146, suggesting that both genes, CD146 and VIM may be directly controlled by the same mechanism or regulate one another. Conclusions The analysis points a potential route for research on the CD146 gene expression, which may lead to understanding of its regulation in breast cancer, contributing to the development of new therapeutic strategies targeting highly metastatic breast cancer cells.
19
Inoue, A., N. Yoshida, Y. Omoto, S. Oguchi, T. Yamori, R. Kiyama, and S. Hayashi. "Development of cDNA microarray for expression profiling of estrogen-responsive genes." Journal of Molecular Endocrinology 29, no. 2 (October 1, 2002): 175–92. http://dx.doi.org/10.1677/jme.0.0290175.
Full textAbstract:
Estrogen plays an important role in many physiological events including carcinogenesis and the development of human breast cancer. However, the molecular mechanisms of estrogen signaling in cancers have not been clarified hitherto and accurate therapeutic prediction of breast cancer is earnestly desired. We first carried out estrogen-responsive expression profiling of approximately 9000 genes in estrogen receptor-positive human MCF-7 breast cancer cells. Based on the results, estrogen-responsive genes were selected for production of a custom-made cDNA microarray. Using a microarray consisting of the narrowed-down gene subset, we first analyzed the time course of the estrogen-responsive gene expression profiles in MCF-7 cells, resulting in subdivision of the genes up-regulated by estrogen into early-responsive and late-responsive genes. The expression patterns of several genes were confirmed by Northern blot analysis. We also analyzed the effects of the estrogen antagonists ICI 182780 and 4-hydroxytamoxifen (OHT) on the estrogen-responsive gene expression profiles in MCF-7 cells. While the regulation of most of the genes by estrogen was completely abolished by ICI 182780, some genes were partially regulated by estrogen even in the presence of OHT. Furthermore, the estrogen-responsive gene expression profiles of twelve cancer cell lines derived from the breast, ovary, stomach and other tissues were obtained and analyzed by hierarchical clustering including the profiles in MCF-7 cells. Several genes also showed up-regulation or down-regulation by estrogen in cell lines other than MCF-7 cells. The significance of the estrogen-responsive genes identified in these analyses concerning the nature of cancer is discussed.
20
Ward, Ashley Vanessa, Shawna B. Matthews, and Carol A. Sartorius. "3300 Progesterone receptor alters lipid biology in luminal breast cancer." Journal of Clinical and Translational Science 3, s1 (March 2019): 19. http://dx.doi.org/10.1017/cts.2019.46.
Full textAbstract:
OBJECTIVES/SPECIFIC AIMS: These studies seek to evaluate hormonal regulation of luminal breast cancer lipid metabolism and to identify targetable progesterone-mediated changes in lipid biology that contribute to therapeutic resistance in breast cancer. METHODS/STUDY POPULATION: Established and patient-derived luminal breast cancer cell lines, which express ER and PR, were used for this study. RNA transcript and protein expression levels were evaluated by qRT-PCR and immunoblot, respectively. Broad scale lipidomics of progesterone-treated cells was conducted via ultra-high pressure liquid chromatography-mass spectrometry (UHPLC-MS) through the UCD Skaggs School of Pharmacy Mass Spectrometry Core. RESULTS/ANTICIPATED RESULTS: Data mining of previously published microarray data of CK5+ and CK5− syngeneic cancer sublines revealed that CK5+ cells have increased expression of lipid processing genes, including LPL and PPARG. As progestin treatment induces a subpopulation of cells to turn on CK5 expression in luminal breast cancers, UHPLC-MS-based lipidomics analysis will expose whether modulation of the lipid landscape occurs in all cells with progesterone treatment, or whether this phenomenon is heightened specifically in CK5+ cells. I also expect that ER+ breast cancers with progestin induced-altered lipid content, such as lipid droplet formation, will evade therapy-induced death. DISCUSSION/SIGNIFICANCE OF IMPACT: There are numerous approved and developmental therapeutics targeting lipid biology. By determining if progestins alter lipid metabolic genes specifically in CK5+ CSCs, which are endocrine resistant, strategies may be devised to target these resistant cells using combination therapy in conjunction with existing therapies to prevent tumor recurrence.
21
Cobleigh, Melody A., Molly DiScala, Matthew S. Najor, Timothy Yung, and Abde M. Abukhdeir. "STAT6 expression and trastuzumab resistance in HER2+ breast cancer." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e13006-e13006. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e13006.
Full textAbstract:
e13006 Background: Approximately 20% of breast cancers are HER2-positive. Trastuzumab has improved patient outcomes significantly for these cancers. However, acquired resistance occurs in almost all patients with metastatic breast cancer. Therefore, identifying molecular changes that are associated with trastuzumab resistance is worthwhile. STAT6 is a transcription factor that regulates a variety of genes involved in cell cycle regulation, growth inhibition, and apoptosis. STAT6 expression is lost in approximately 3% of breast cancers, but little work has been done in the context of trastuzumab resistance in breast cancer. Methods: In isogenic cell line pairs, we observed that trastuzumab-resistant cells expressed significantly lower levels of STAT6 compared to trastuzumab-sensitive cells. Therefore, in order to study the consequences of STAT6 loss in HER2+ breast cancer, we knocked out both alleles of the STAT6 gene using somatic cell gene targeting. Results: We observed that loss of STAT6 resulted in resistance to trastuzumab treatment in HER2-over-expressing cells. Additionally, loss of STAT6 resulted in anchorage-independent growth and changed expression of several genes involved in epithelial to mesenchymal transition. Functional studies revealed that STAT6 loss caused a non-tumorigenic human breast cell line to form tumors in mice. Conclusions: Loss of STAT6 in breast cells results in enhanced growth properties and resistance to trastuzumab. This study suggests that STAT6 may play a role in the pathophysiology of HER2+ human breast cancer. Disclaimer: The work herein was completed while AMA was a faculty member at Rush University. AMA is currently an employee with the U.S. Food and Drug Administration. The views and data in this publication do not reflect the opinions of the U.S. Government or The U.S. Food and Drug Administration.
22
Chen, Yongqiang, Ruobing Wang, Shujun Huang, Elizabeth S. Henson, Jayce Bi, and Spencer B. Gibson. "Erb-b2 Receptor Tyrosine Kinase 2 (ERBB2) Promotes ATG12-Dependent Autophagy Contributing to Treatment Resistance of Breast Cancer Cells." Cancers 13, no. 5 (March 2, 2021): 1038. http://dx.doi.org/10.3390/cancers13051038.
Full textAbstract:
The epidermal growth factor receptor (EGFR) family member erb-b2 receptor tyrosine kinase 2 (ERBB2) is overexpressed in many types of cancers leading to (radio- and chemotherapy) treatment resistance, whereas the underlying mechanisms are still unclear. Autophagy is known to contribute to cancer treatment resistance. In this study, we demonstrate that ERBB2 increases the expression of different autophagy genes including ATG12 (autophagy-related 12) and promotes ATG12-dependent autophagy. We clarify that lapatinib, a dual inhibitor for EGFR and ERBB2, promoted autophagy in cells expressing only EGFR but inhibited autophagy in cells expressing only ERBB2. Furthermore, breast cancer database analysis of 35 genes in the canonical autophagy pathway shows that the upregulation of ATG12 and MAP1LC3B is associated with a low relapse-free survival probability of patients with ERBB2-positive breast tumors following treatments. Downregulation of ERBB2 or ATG12 increased cell death induced by chemotherapy drugs in ERBB2-positive breast cancer cells, whereas upregulation of ERBB2 or ATG12 decreased the cell death in ERBB2-negative breast cancer cells. Finally, ERBB2 antibody treatment led to reduced expression of ATG12 and autophagy inhibition increasing drug or starvation-induced cell death in ERBB2-positive breast cancer cells. Taken together, this study provides a novel approach for the treatment of ERBB2-positive breast cancer by targeting ATG12-dependent autophagy.
23
El-Masry, Omar S., Arafat Goja, Mostafa Rateb, Amani Y. Owaidah, and Khaldoon Alsamman. "RNA sequencing identified novel target genes for Adansonia digitata in breast and colon cancer cells." Science Progress 104, no. 3 (July 2021): 003685042110320. http://dx.doi.org/10.1177/00368504211032084.
Full textAbstract:
Adansonia digitata exhibits numerous beneficial effects. In the current study, we investigated the anti-cancer effects of four different extracts of A. digitata (polar and non-polar extracts of fruit powder and fibers) on the proliferation of human colon cancer (HCT116), human breast cancer (MCF-7), and human ovarian cancer (OVCAR-3 and OVCAR-4) cell lines. RNA sequencing revealed the influence of the effective A. digitata fraction on the gene expression profiles of responsive cells. The results indicated that only the polar extract of the A. digitata fibers exhibited anti-proliferative activities against HCT116 and MCF-7 cells, but not ovarian cancer cells. Moreover, the polar extract of the fibers resulted in the modulation of the expression of multiple genes in HCT116 and MCF-7 cells. We propose that casein kinase 2 alpha 3 ( CSNK2A3) is a novel casein kinase 2 ( CSNK2) isoform in HCT116 cells and report, for the first time, the potential involvement of FYVE, RhoGEF, and PH domain-containing 3 ( FGD3) in colon cancer. Together, these findings provide evidence supporting the anti-cancer potential of the polar extract of A. digitata fibers in this experimental model of breast and colon cancers.
24
Atalay, Arzu, Tim Crook, Mehmet Ozturk, and Isik G. Yulug. "Identification of genes induced by BRCA1 in breast cancer cells." Biochemical and Biophysical Research Communications 299, no. 5 (December 2002): 839–46. http://dx.doi.org/10.1016/s0006-291x(02)02751-1.
Full text
25
Meech, Robyn, Dong Gui Hu, Apichaya Chanawong, Lu Lu, Nurul Mubarokah, Ross A. McKinnon, and Peter I. Mackenzie. "Regulation of UDP glucuronosyltransferase 2B genes in breast cancer cells." Drug Metabolism and Pharmacokinetics 33, no. 1 (January 2018): S55. http://dx.doi.org/10.1016/j.dmpk.2017.11.188.
Full text
26
Yunita, Elvira. "Epigenetic Regulation of Breast Cancer Stem Cells." Biomedical Journal of Indonesia 7, no. 2 (March 22, 2021): 270–84. http://dx.doi.org/10.32539/bji.v7i2.289.
Full textAbstract:
Breast cancer arises as a result of abnormal breast cells forming at an uncontrolled rate. Death in this case of breast cancer is due to the ability of cancer cells to adapt so that it can have an effect on metastasis and recurrence of cancer that was previously thought to have been resolved. The results showed, there is a stem cell population in breast cancer cases which will cause breast cancer to become increasingly difficult to treat. Such cells are known as breast cancer stem cells.Breast cancer cells have the ability to differentiate and contribute greatly to the breast cancer program, as well as to resistance to therapy. Therefore, epigeneticregulation of breast cancer cells is important to study in order to overcome cancer so that it can overcome progression and resistance to cancer therapy being carried out.Epigenetic regulation that has been known in cancer cases includes DNA methylation, histone acetylation, histone methylation and epigenetic regulation by miRNA. DNA methylation is the addition of a methyl group to the nitrogen base of DNA cytosine which will force the DNA transcription process. Acetylation of theaddition of an acetyl group at the end of the histone causes reduced chromatin condensation so that it will activate the transcription process. Methylation histones will also suppress transcription so that genes cannot be expressed. In addition, there is also a small RNA molecule known as miRNA which can bind to the transcribed mRNA. This binding will cause the mRNA to degrade or inhibit its translation.
27
Shirkavand, Atefeh, Zahra N. Boroujeni, and Seyed A. Aleyasin. "Solanum nigrum Anticancer Effect Through Epigenetic Modulations in Breast Cancer Cell Lines." Current Cancer Therapy Reviews 16, no. 2 (June 9, 2020): 121–26. http://dx.doi.org/10.2174/1573394715666190101114541.
Full textAbstract:
Background: DNA methylation plays an important role in the regulation of gene expression in mammalian cells and often occurs at CpG islands in the genome. It is more reversible than genetic variations and has therefore attracted much attention for the treatment of many diseases, especially cancer. In the present study, we investigated the effect of Solanum nigrum Extract (SNE) on the methylation status of the VIM and CXCR4 genes in breast cancer cell lines. Methods: The Trypan blue assay was used to study the effect of SNE at various concentrations of 0, 0.1, 1.5, 2.5, 3.5 and 5 mg/ml for 48 h on the survival of three human breast cancer cell lines MCF7, MDA-MB-468, MDA-MB-231. Methylation status of VIM and CXCR4 genes in breast cancer cell lines was assessed by Methylation-Specific PCR (MSP) method. Also, methylation changes of VIM and CXCR4 genes in breast cancer cell lines after treatment with 0.1 mg/ml of SNE for 6 days were analyzed by MSP method. To confirm the effect of SNE on methylation of VIM and CXCR4 genes, Real-Time PCR was performed. Results: The Trypan blue assay results indicated that treatment with SNE reduced cell viability in a dose-dependent manner in breast cancer cells. Our results showed that treatment of breast cancer cells with 0.1 mg/ml of SNE hypermethylated the VIM, CXCR4 genes and significantly reduced the expression levels of their mRNA (P<0.05). Conclusion: Our findings reveal for the first time the impact of SNE on the methylation of breast cancer cells.
28
Eiro, Noemi, Sandra Cid, Nuria Aguado, María Fraile, Nagore de Pablo, Berta Fernández, Francisco Domínguez, Luis O. González, and Francisco J. Vizoso. "MMP1 and MMP11 Expression in Peripheral Blood Mononuclear Cells upon Their Interaction with Breast Cancer Cells and Fibroblasts." International Journal of Molecular Sciences 22, no. 1 (December 31, 2020): 371. http://dx.doi.org/10.3390/ijms22010371.
Full textAbstract:
Tumor-infiltrating immune cells phenotype is associated with tumor progression. However, little is known about the phenotype of the peripheral blood mononuclear cells (PBMC) from breast cancer patients. We investigated MMP1 and MMP11 expression in PBMC from breast cancer patients and we analyzed gene expression changes upon their interaction with cancer cells and cancer-associated fibroblasts (CAF). We measured the impact of PBMC on proinflammatory gene expression in breast cancer cells, normal fibroblast (NF), and CAF and the impact on proliferation and invasiveness capacity of breast cancer cells. Gene expression of MMP1 and MMP11 in PBMC from breast cancer patients (n = 54) and control (n = 28); expression of IL1A, IL6, IL17, IFNβ, and NFĸB in breast cancer cell lines (MCF-7 and MDA-MB-231); and, additionally, IL10 and MMP11 in CAF and NF were analyzed by qRT-PCR before and after co-culture. Our results show the existence of a subpopulation of breast cancer patients (25.9%) with very high levels of MMP11 gene expression in PBMC. Also, gene expression of MMP1 and MMP11 increases in PBMC after co-culture with breast cancer cell lines, NF or CAF. PBMC from healthy or breast cancer patients induce an increased proliferation rate on MCF-7 and an increased invasiveness capacity of MDA-MB-231. Finally, we show a differential expression profile of inflammatory genes in NF and CAF when co-cultured with control or breast cancer PBMC. We have observed that MMPs’ expression in PBMC is regulated by the microenvironment, while the expression of inflammatory genes in NF or CAF is differentially regulated by PBMC. These findings confirm the importance of the crosstalk between stromal cells and suggest that PBMC would play a role in promoting aggressive tumor behavior.
29
Ying, Xuexiang, Yunpo Sun, and Pingqing He. "Bone Morphogenetic Protein-7 Inhibits EMT-Associated Genes in Breast Cancer." Cellular Physiology and Biochemistry 37, no. 4 (2015): 1271–78. http://dx.doi.org/10.1159/000430249.
Full textAbstract:
Background/Aims: Bone morphogenetic protein-7 (BMP7) has been shown to reduce the severity of injury-induced fibrosis through counteracting the fibrotic effects of transforming growth factor β 1 (TGFβ1). However, this model in the carcinogenesis of breast cancer is unknown. Methods: We analyzed the effects of BMP7 and TGFβ1 on gene transcripts and protein levels of EMT-related factors in breast cancer cells by RT-qPCR and Western blot, respectively. The effects of BMP7 and TGFβ1 on cell invasiveness and migration were evaluated by scratch wound healing assay and transwell cell migration assay. The cell growth was measured by MTT assay. Results: BMP7 did not alter the TGFβ1-stimulated phosphorylation of TGFβ receptor, but significantly inhibited the TGFβ1-activated epithelial-mesenchymal transition (EMT)-related genes in breast cancer cells, resulting in a significant reduction in TGFβ1-triggered cell growth and cell metastasis. Conclusion: Our data suggest that besides being a well-known antagonist for TGFβ1 in fibrosis, BMP7 may also antagonize TGFβ1 in tumorigenesis-associated EMT in breast cancer. Thus, BMP7 may be a promising therapeutic target for treating breast cancer.
30
Zhang, F., Y. Xu, C. Song, Y. Ma, F. Nan, H. Wang, S. Lin, M. Huang, and Y. Zhang. "Regulational effects of breast cancer stromal cells and normal breast stromal cells on MCF-7 mammosphere formation." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 1056. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.1056.
Full textAbstract:
1056 Background: It is well known that microenvironment plays an important role in tumor progression so we investigated the regulatory effects of breast cancer stromal cells (BCSCs) and normal breast stromal cells (NBSCs) as microenvironment on MCF-7 mammosphere formation. Methods: MCF-7 cells were cultured in suspension to generate mammospheres. The proportion of CD44+CD24- cells was assessed by flow cytometry and the expression of Wint1, notch1, β-catenin, CXCR4, SOX2, and ALDH3A1 was detected by real-time PCR. The stromal cells were purified and identified by immumohistochemistry. BCSCs or NBSCs and MCF-7 cells were co-cultured via Transwell system, the volumes and numbers of mammospheres and the mammosphere-forming efficiency (MFE) were calculated and the expression of Wnt1, β-catenin, Notch1 were detected. Results: The proportion of CD44+CD24- cells in mammospheres and MCF-7 cells was 10.4% and 2.1% (p < 0.05), respectively. Real-time PCR analysis suggested that Wint1, notch1, β-catenin, CXCR4, SOX2, and ALDH3A1 genes in the mammosphere cells were with higher levels than MCF-7 cells by about 2.25, 2.45, 1.72, 4.68, 4.25, 5.38 fold, respectively (p < 0.01). The stromal cells purified were identified as fibroblasts by α-SMA,Vimentin and fibroblast special protein antibody via immumohistochemistry. The time of mammosphere's formation was earlier, the volumes of mammospheres were bigger, and the MFE was higher than control group. The expressions of Wnt1 in co-culture group were significantly upregulated 1.27, 3.18 folds than control group, respectively, while the β-catenin was 1.22, 1.75 folds; Notch1 was 1.31, 2.09 folds; and CXCR4 was 1.73, 2.77 folds, respectively. Conclusions: Mammosphere cells contained higher propotion of breast cancer stem cells and expressed higher levels of cancer stem cell related genes. BCSCs can promote the mammosphere-forming efficiency and upregulate the expression of cancer stem cell related genes. No significant financial relationships to disclose.
31
Chu, Pei-Yi, Ming-Feng Hou, Ji-Ching Lai, Long-Fong Chen, and Chang-Shen Lin. "Cell Reprogramming in Tumorigenesis and Its Therapeutic Implications for Breast Cancer." International Journal of Molecular Sciences 20, no. 8 (April 12, 2019): 1827. http://dx.doi.org/10.3390/ijms20081827.
Full textAbstract:
Breast cancer is the most common malignancy in women worldwide and can be categorized into several subtypes according to histopathological parameters or genomic signatures. Such heterogeneity of breast cancer can arise from the reactivation of mammary stem cells in situ during tumorigenesis. Moreover, different breast cancer subtypes exhibit varieties of cancer incidence, therapeutic response, and patient prognosis, suggesting that a specific therapeutic protocol is required for each breast cancer subtype. Recent studies using molecular and cellular assays identified a link between specific genetic/epigenetic alterations and distinct cells of origin of breast cancer subtypes. These alterations include oncogenes, tumor suppressor genes, and cell-lineage determinants, which can induce cell reprogramming (dedifferentiation and transdifferentiation) among two lineage-committed mammary epithelial cells, namely basal and luminal cells. The interconversion of cell states through cell reprogramming into the intermediates of mammary stem cells can give rise to heterogeneous breast cancers that complicate effective therapies of breast cancer. A better understanding of mechanisms underlying cell reprogramming in breast cancer can help in not only elucidating tumorigenesis but also developing therapeutics for breast cancer. This review introduces recent findings on cancer gene-mediated cell reprogramming in breast cancer and discusses the therapeutic potential of targeting cell reprogramming.
32
Lu, Xiangdong, Jingjing Ma, Jiahui Chu, Qing Shao, Yao Zhang, Guangping Lu, Jun Li, et al. "MiR-129-5p Sensitizes the Response of Her-2 Positive Breast Cancer to Trastuzumab by Reducing Rps6." Cellular Physiology and Biochemistry 44, no. 6 (2017): 2346–56. http://dx.doi.org/10.1159/000486122.
Full textAbstract:
Background/Aims: Trastuzumab is an important treatment used for patients with Her-2-positive breast cancer, but an increasing incidence of trastuzumab resistance has been observed clinically during the past decade. Aberrant microRNA (miR) expression levels are correlated with prognosis and response to trastuzumab in breast cancer. MiR-129-5p is downregulated in trastuzumab-resistant human breast cancer cells (JIMT-1), but its potential function and underlying mechanism remain unclear. Methods: Quantitative RT-PCR (qRT-PCR) was used to determine the expression levels of miR-129-5p and its potential target genes. The effects of miR-129-5p on cell responses to trastuzumab were analyzed by CCK-8 and flow cytometry assays in Her-2-positive breast cancer cells (SKBR-3 and JIMT-1). Bio-informatics analyses were performed to predict target genes of miR-129-5p, and luciferase assays were carried out to confirm the binding of miR-129-5p and rpS6. Results: MiR-129-5p, which was downregulated and predicted to target rpS6 in trastuzumab-resistant breast cancer cells, enhanced the sensitivity of breast cancer cells to trastuzumab by reducing the expression of rpS6. Moreover, the overexpression of rpS6 reversed the sensitivity of cells to trastuzumab induced by miR-129-5p. Conclusions: MiR-129-5p sensitized Her-2-positive breast cancer to trastuzumab by downregulating rpS6. These findings provide novel insights into the common role of rpS6 and its related molecular mechanisms in mediating trastuzumab-resistance in Her-2-positive breast cancers.
33
Post, Annemarie E. M., Johan Bussink, Fred C. G. J. Sweep, and Paul N. Span. "Changes in DNA Damage Repair Gene Expression and Cell Cycle Gene Expression Do Not Explain Radioresistance in Tamoxifen-Resistant Breast Cancer." Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 28, no. 1 (February 7, 2020): 33–40. http://dx.doi.org/10.3727/096504019x15555794826018.
Full textAbstract:
Tamoxifen-induced radioresistance, reported in vitro, might pose a problem for patients who receive neoadjuvant tamoxifen treatment and subsequently receive radiotherapy after surgery. Previous studies suggested that DNA damage repair or cell cycle genes are involved, and could therefore be targeted to preclude the occurrence of cross-resistance. We aimed to characterize the observed cross-resistance by investigating gene expression of DNA damage repair genes and cell cycle genes in estrogen receptor-positive MCF-7 breast cancer cells that were cultured to tamoxifen resistance. RNA sequencing was performed, and expression of genes characteristic for several DNA damage repair pathways was investigated, as well as expression of genes involved in different phases of the cell cycle. The association of differentially expressed genes with outcome after radiotherapy was assessed in silico in a large breast cancer cohort. None of the DNA damage repair pathways showed differential gene expression in tamoxifen-resistant cells compared to wild-type cells. Two DNA damage repair genes were more than two times upregulated (NEIL1 and EME2), and three DNA damage repair genes were more than two times downregulated (PCNA, BRIP1, and BARD1). However, these were not associated with outcome after radiotherapy in the TCGA breast cancer cohort. Genes involved in G1, G1/S, G2, and G2/M phases were lower expressed in tamoxifen-resistant cells compared to wild-type cells. Individual genes that were more than two times upregulated (MAPK13) or downregulated (E2F2, CKS2, GINS2, PCNA, MCM5, and EIF5A2) were not associated with response to radiotherapy in the patient cohort investigated. We assessed the expression of DNA damage repair genes and cell cycle genes in tamoxifen-resistant breast cancer cells. Though several genes in both pathways were differentially expressed, these could not explain the cross-resistance for irradiation in these cells, since no association to response to radiotherapy in the TCGA breast cancer cohort was found.
34
Dharmarajan, A., N. Zeps, and S. McLaren. "003.Expression of secreted frizzled related protein-4 (sFRP-4) and associated Wnt signalling in cancer and apoptosis." Reproduction, Fertility and Development 17, no. 9 (2005): 63. http://dx.doi.org/10.1071/srb05abs003.
Full textAbstract:
We examined the interplay between Wnt and secreted frizzled related protein-4 (sFRP4) in estradiol induced cell growth in breast cancer cells (MCF-7), and also determined the in vivo distribution of sFRP-4 in human breast cancer. MCF-7 cells were treated with estradiol, sFRP-4 conditioned media and a combination of the two. Real-time RT-PCR and Western blot analysis were used to determine the expression of the sFRP-4 and its associated Wnt signalling molecules following treatment. Immunohistochemistry was performed to examine sFRP-4 expression patterns in human breast cancers. Estradiol treatment up-regulated the expression of the Wnt signalling genes Wnt-10b, beta-catenin and fz-4 (P < 0.001 for all genes). This up-regulation was not associated with an increase in the Wnt signalling pathway as measured by the levels of active beta-catenin. sFRP-4 conditioned media reduced MCF-7 cell proliferation, down-regulated the Wnt signalling genes beta-catenin and fz-4 as well as down-regulating wnt signalling activity. sFRP-4 was able to reduce the proliferation of estradiol stimulated MCF-7 cells. Cytoplasmic sFRP-4 protein was expressed in all breast tumours examined, with intense staining evident in the lobular carcinoma in situ and the ductal carcinoma. These data demonstrate that sFRP-4 is a potent inhibitor of the Wnt signalling pathway in MCF-7 cells, acting not only to down-regulate the activity of the wnt signalling pathway, but also down-regulate the transcription of Wnt signalling genes. The results of these in vitro and immunohistochemical experiments warrant further investigation as to whether sFRP-4 expression can be indicative of prognosis in human breast cancer. In addition to breast cancer, we have also examined the role of sFRP-4 in other cancers such as ovarian and prostate.
35
Chimonidou, Maria, Areti Strati, Alexandra Tzitzira, Georgia Sotiropoulou, Nikos Malamos, Vasilis Georgoulias, and Evi S. Lianidou. "DNA Methylation of Tumor Suppressor and Metastasis Suppressor Genes in Circulating Tumor Cells." Clinical Chemistry 57, no. 8 (August 1, 2011): 1169–77. http://dx.doi.org/10.1373/clinchem.2011.165902.
Full textAbstract:
BACKGROUND Circulating tumor cells (CTCs) are associated with prognosis in a variety of human cancers and have been proposed as a liquid biopsy for follow-up examinations. We show that tumor suppressor and metastasis suppressor genes are epigenetically silenced in CTCs isolated from peripheral blood of breast cancer patients. METHODS We obtained peripheral blood from 56 patients with operable breast cancer, 27 patients with verified metastasis, and 23 healthy individuals. We tested DNA extracted from the EpCAM-positive immunomagnetically selected CTC fraction for the presence of methylated and unmethylated CST6, BRMS1, and SOX17 promoter sequences by methylation-specific PCR (MSP). All samples were checked for KRT19 (keratin 19, formerly CK-19) expression by reverse-transcription quantitative PCR. RESULTS In CTCs of patients with operable breast cancer, promoter methylation of CST6 was observed in 17.9%, BRMS1 in 32.1%, and SOX17 in 53.6% of patients. In CTCs of patients with verified metastasis, promoter methylation of CST6 was observed in 37.0%, BRMS1 in 44.4%, and SOX17 in 74.1%. In healthy individuals, promoter methylation of CST6 was observed in 4.3%, BRMS1 in 8.7%, and SOX17 in 4.3%. DNA methylation of these genes for both operable and metastatic breast cancer was significantly different from that of the control population. CONCLUSIONS DNA methylation of tumor suppressor and metastasis suppressor genes is a hallmark of CTCs and confirms their heterogeneity. Our findings add a new dimension to the molecular characterization of CTCs and may underlie the acquisition of malignant properties, including their stem-like phenotype.
36
Park, Yun-Yong, Sung Yun Jung, Nicholas B. Jennings, Cristian Rodriguez-Aguayo, Guang Peng, Se-Ran Lee, Sang Bae Kim, et al. "FOXM1 mediates Dox resistance in breast cancer by enhancing DNA repair." Carcinogenesis 33, no. 10 (May 10, 2012): 1843–53. http://dx.doi.org/10.1093/carcin/bgs167.
Full textAbstract:
Abstract Transcription factors are direct effectors of altered signaling pathways in cancer and frequently determine clinical outcomes in cancer patients. To uncover new transcription factors that would determine clinical outcomes in breast cancer, we systematically analyzed gene expression data from breast cancer patients. Our results revealed that Forkhead box protein M1 (FOXM1) is the top-ranked survival-associated transcription factor in patients with triple-negative breast cancer. Surprisingly, silencing FOXM1 expression led breast cancer cells to become more sensitive to doxorubicin (Dox). We found that FOXM1-dependent resistance to Dox is mediated by regulating DNA repair genes. We further demonstrated that NFκB1 interacts with FOXM1 in the presence of Dox to protect breast cancer cells from DNA damage. Finally, silencing FOXM1 expression in breast cancer cells in a mouse xenograft model significantly sensitized the cells to Dox. Our systematic approaches identified an unexpected role of FOXM1 in Dox resistance by regulating DNA repair genes, and our findings provide mechanistic insights into how FOXM1 mediates resistance to Dox and evidence that FOXM1 may be a promising therapeutic target for sensitizing breast cancer cells to Dox.
37
Lorico, Aurelio, and Germana Rappa. "Phenotypic Heterogeneity of Breast Cancer Stem Cells." Journal of Oncology 2011 (2011): 1–6. http://dx.doi.org/10.1155/2011/135039.
Full textAbstract:
Many types of tumors are organized in a hierarchy of heterogeneous cell populations, with only a small proportion of cancer stem cells (CSCs) capable of sustaining tumor formation and growth, giving rise to differentiated cells, which form the bulk of the tumor. Proof of the existence of CSC comes from clinical experience with germ-cell cancers, where the elimination of a subset of undifferentiated cells can cure patients (Horwich et al., 2006), and from the study of leukemic cells (Bonnet and Dick, 1997; Lapidot et al., 1994; and Yilmaz et al., 2006). The discovery of CSC in leukemias as well as in many solid malignancies, including breast carcinoma (Al-Hajj et al. 2003; Fang et al., 2005; Hemmati et al., 2003; Kim et al., 2005; Lawson et al., 2007; Li et al., 2007; Ricci-Vitiani et al., 2007; Singh et al., 2003; and Xin et al., 2005), has suggested a unifying CSC theory of cancer development. The reported general insensitivity of CSC to chemotherapy and radiation treatment (Bao et al., 2006) has suggested that current anticancer drugs, which inhibit bulk replicating cancer cells, may not effectively inhibit CSC. The clinical relevance of targeting CSC-associated genes is supported by several recent studies, including CD44 targeting for treatment of acute myeloid leukemia (Jin et al., 2006), CD24 targeting for treatment of colon and pancreatic cancer (Sagiv et al., 2008), and CD133 targeting for hepatocellular and gastric cancer (Smith et al., 2008). One promising approach is to target CSC survival signaling pathways, where leukemia stem cell research has already made some progress (Mikkola et al., 2010).
38
Xiang, S., L. Mao, T. Duplessis, L. Yuan, R. Dauchy, E. Dauchy, D. E. Blask, T. Frasch, and S. M. Hill. "Oscillation of Clock and Clock Controlled Genes Induced by Serum Shock in Human Breast Epithelial and Breast Cancer Cells: Regulation by Melatonin." Breast Cancer: Basic and Clinical Research 6 (January 2012): BCBCR.S9673. http://dx.doi.org/10.4137/bcbcr.s9673.
Full textAbstract:
This study investigates differences in expression of clock and clock-controlled genes (CCGs) between human breast epithelial and breast cancer cells and breast tumor xenografts in circadian intact rats and examines if the pineal hormone melatonin influences clock gene and CCG expression. Oscillation of clock gene expression was not observed under standard growth conditions in vitro, however, serum shock (50% horse serum for 2 h) induced oscillation of clock gene and CCG expression in MCF-10A cells, which was repressed or disrupted in MCF-7 cells. Melatonin administration following serum shock differentially suppressed or induced clock gene (Bmal1 and Per2) and CCG expression in MCF10A and MCF-7 cells. These studies demonstrate the lack of rhythmic expression of clock genes and CCGs of cells in vitro and that transplantation of breast cancer cells as xenografts into circadian competent hosts re-establishes a circadian rhythm in the peripheral clock genes of tumor cells.
39
Shiu, Li Yen, Chia Hua Liang, Li Ching Chang, Hamm Ming Sheu, Eing Mei Tsai, and Kou Wha Kuo. "Solamargine induces apoptosis and enhances susceptibility to trastuzumab and epirubicin in breast cancer cells with low or high expression levels of HER2/neu." Bioscience Reports 29, no. 1 (December 10, 2008): 35–45. http://dx.doi.org/10.1042/bsr20080028.
Full textAbstract:
Trastuzumab is used for breast cancer patients with high expression levels of HER2 (human epidermal growth factor receptor 2)/neu; however, it has no effect on cancers with low levels of HER2/neu. SM (solamargine), a major steroidal alkaloid glycoside purified from Solanum incanum, triggered apoptosis of breast cancer cells (MCF-7 and SK-BR-3 cells) and non-cancerous breast epithelial cells (HBL-100 cells) within 3 h. To extend the application of trastuzumab in breast cancer patients, the regulation of HER2/neu expression by SM was investigated. SM significantly up-regulates HER2/neu expression in breast cancer cells with low and high expression levels of HER2/neu, and synergistically enhanced the effect of trastuzumab in inhibiting cell proliferation. Additionally, HER2/neu and TOP2A [TopoII (topoisomerase II) α] genes share the same amplicon on an identical chromosome. Notably, SM co-regulates HER2/neu and TopoIIα expression markedly, and enhances TopoII inhibitor–EPI (epirubicin)-induced cytotoxicity to breast cancer cells.
40
Chuffa, Luiz Gustavo de Almeida, Fábio Rodrigues Ferreira Seiva, Maira Smaniotto Cucielo, Henrique Spaulonci Silveira, Russel J. Reiter, and Luiz Antonio Lupi. "Clock genes and the role of melatonin in cancer cells: an overview." Melatonin Research 2, no. 2 (June 12, 2019): 133–57. http://dx.doi.org/10.32794/mr11250026.
Full textAbstract:
Circadian rhythms control most biological processes in every organism and their disruption or an aberrant function in the expression of clock genes are associated with a number of cancers including some hormone-dependent and independent cancers. The processes involved in carcinogenesis and tumor progression are complex, but understanding the daily profiles of the core clock genes and their clock-controlled genes is essential to evaluate specifically the molecular program of the cancer phenotype; this may be helpful in providing a more realistic strategy for both diagnosis and treatment during the course of the disease. Because melatonin production and secretion oscillates rhythmically through the light:dark cycle and is related to the circadian machinery genes (Clock, Bmal1, Periods, and Cryptochromes), its regulatory role on clock genes in cancer cells may bring additional evidence regarding the mechanism(s) by which melatonin is involved. Mechanistically, melatonin acts via proteasome inhibition and sirtuins to indirectly modulate clock genes in cancer; however, melatonin seems to be capable of directly altering the expression of clock genes to affect cancer development. Depending on cancer cell type, melatonin might up or downregulate specific clock genes to control cell cycle, survival, repair mechanisms, etc. In parallel, melatonin exerts pro-apoptotic, anti-proliferative and pro-oxidative effects, metabolic shifting, reduction in neovasculogenesis and inflammation, and restores chemosensitivity of cancer cells. Finally, melatonin improves the life quality of patients. This review focuses on the main functions of melatonin on clock genes, and reviews, from a clinical and experimental standpoint, how melatonin regulates the expression of clock genes in some prevalent cancer types such as breast, prostate, liver, and colon cancers, leukemia and melanoma. We further emphasized possible signaling mechanisms whereby melatonin interferes with clockwork genes and circadian-controlled genes within cancer cells.
41
Cichon, Magdalena A., Celeste M. Nelson, and Derek C. Radisky. "Regulation of Epithelial-Mesenchymal Transition in Breast Cancer Cells by Cell Contact and Adhesion." Cancer Informatics 14s3 (January 2015): CIN.S18965. http://dx.doi.org/10.4137/cin.s18965.
Full textAbstract:
Epithelial-mesenchymal transition (EMT) is a physiological program that is activated during cancer cell invasion and metastasis. We show here that EMT-related processes are linked to a broad and conserved program of transcriptional alterations that are influenced by cell contact and adhesion. Using cultured human breast cancer and mouse mammary epithelial cells, we find that reduced cell density, conditions under which cell contact is reduced, leads to reduced expression of genes associated with mammary epithelial cell differentiation and increased expression of genes associated with breast cancer. We further find that treatment of cells with matrix metalloproteinase-3 (MMP-3), an inducer of EMT, interrupts a defined subset of cell contact-regulated genes, including genes encoding a variety of RNA splicing proteins known to regulate the expression of Rac1b, an activated splice isoform of Rac1 known to be a key mediator of MMP-3-induced EMT in breast, lung, and pancreas. These results provide new insights into how MMPs act in cancer progression and how loss of cell-cell interactions is a key step in the earliest stages of cancer development.
42
Meaburn, Karen J., Prabhakar R. Gudla, Sameena Khan, Stephen J. Lockett, and Tom Misteli. "Disease-specific gene repositioning in breast cancer." Journal of Cell Biology 187, no. 6 (December 7, 2009): 801–12. http://dx.doi.org/10.1083/jcb.200909127.
Full textAbstract:
Genomes are nonrandomly organized within the three-dimensional space of the cell nucleus. Here, we have identified several genes whose nuclear positions are altered in human invasive breast cancer compared with normal breast tissue. The changes in positioning are gene specific and are not a reflection of genomic instability within the cancer tissue. Repositioning events are specific to cancer and do not generally occur in noncancerous breast disease. Moreover, we show that the spatial positions of genes are highly consistent between individuals. Our data indicate that cancer cells have disease-specific gene distributions. These interphase gene positioning patterns may be used to identify cancer tissues.
43
Mishra, Akanksha, Maria Bonello, Adam Byron, Simon P. Langdon, and Andrew H. Sims. "Evaluation of Gene Expression Data From Cybrids and Tumours Highlights Elevated NDRG1-Driven Proliferation in Triple-Negative Breast Cancer." Breast Cancer: Basic and Clinical Research 14 (January 2020): 117822342093444. http://dx.doi.org/10.1177/1178223420934447.
Full textAbstract:
Background: Triple-negative breast cancer is an aggressive type of breast cancer with high risk of recurrence. It is still poorly understood and lacks any targeted therapy, which makes it difficult to treat. Thus, it is important to understand the underlying mechanisms and pathways that are dysregulated in triple-negative breast cancer. Methods: To investigate the role of mitochondria in triple-negative breast cancer progression, we analysed previously reported gene expression data from triple-negative breast cancer cybrids with SUM-159 as the nuclear donor cell and SUM-159 or A1N4 (c-SUM-159, c-A1N4) as the mitochondrial donor cells and with 143B as the nuclear donor cell and MCF-10A or MDA-MB-231 (c-MCF-10A, c-MDA-MB-231) as the mitochondrial donor cells. The role of potential biomarkers in cell proliferation and migration was examined in SUM-159 and MDA-MB-231 cells using sulforhodamine B and wound healing assays. Results: Rank product analysis of cybrid gene expression data identified 149 genes which were significantly up-regulated in the cybrids with mitochondria from the cancer cell line. Analysis of previously reported breast tumour gene expression datasets confirmed 9 of the 149 genes were amplified, up-regulated, or down-regulated in more than 10% of the patients. The genes included NDRG1, PVT1, and EXT1, which are co-located in cytoband 8q24, which is frequently amplified in breast cancer. NDRG1 showed the largest down-regulation in the cybrids with benign mitochondria and was associated with poor prognosis in a breast cancer clinical dataset. Knockdown of NDRG1 expression significantly decreased proliferation of SUM-159 triple-negative breast cancer cells. Conclusions: These results indicate that mitochondria-regulated nuclear gene expression helps breast cancer cells survive and proliferate, consistent with previous work focusing on an Src gene signature which is mitochondria regulated and drives malignancy in breast cancer cybrids. This is the first study to show that mitochondria in triple-negative breast cancer mediate significant up-regulation of a number of genes, and silencing of NDRG1 leads to significant reduction in proliferation.
44
Shi, Ying, Weihua Gong, Xiangrong Gong, Ping Wang, and Xin Zhao. "Genome-wide DNA methylation analysis of breast cancer MCF-7 / Taxol cells with MeDIP-Seq." PLOS ONE 15, no. 12 (December 11, 2020): e0241515. http://dx.doi.org/10.1371/journal.pone.0241515.
Full textAbstract:
Breast cancer (BC) is the most frequently diagnosed tumor in women worldwide. Although the combination of surgery and Taxol chemotherapy can achieve a certain therapeutic effect, patients often develop drug-resistance, resulting in a poor prognosis. Therefore, it is significative to seek the molecular mechanism of chemotherapy resistance. Recent studies have found that abnormal epigenetic regulation in breast cells changes the expression of key genes, which can lead to the occurrence, development, and maintenance of cancer, even related to the development of drug-resistance. Therefore, in this study, we performed methylated DNA immunoprecipitation-sequencing (MeDIP-seq) to reveal the difference in methylation between breast cancer drug-resistant cells and sensitive cells. A total of 55076 differentially methylated genes (DMGs) were detected, including 21061 hypermethylated DMGs and 34015 hypomethylated DMGs. Moreover, Gene Ontology (GO) analysis and KEGG pathway analysis reveal the function and pathway of screening genes. These results indicate that DNA methylation may be involved in regulating the occurrence and development of breast cancer.
45
Kuroiwa, Yuka, Jun Nakayama, Chihiro Adachi, Takafumi Inoue, Shinya Watanabe, and Kentaro Semba. "Proliferative Classification of Intracranially Injected HER2-positive Breast Cancer Cell Lines." Cancers 12, no. 7 (July 6, 2020): 1811. http://dx.doi.org/10.3390/cancers12071811.
Full textAbstract:
HER2 is overexpressed in 25–30% of breast cancers, and approximately 30% of HER2-positive breast cancers metastasize to the brain. Although the incidence of brain metastasis in HER2-positive breast cancer is high, previous studies have been mainly based on cell lines of the triple-negative subtype, and the molecular mechanisms of brain metastasis in HER2-positive breast cancer are unclear. In the present study, we performed intracranial injection using nine HER2-positive breast cancer cell lines to evaluate their proliferative activity in brain tissue. Our results show that UACC-893 and MDA-MB-453 cells rapidly proliferated in the brain parenchyma, while the other seven cell lines moderately or slowly proliferated. Among these nine cell lines, the proliferative activity in brain tissue was not correlated with either the HER2 level or the HER2 phosphorylation status. To extract signature genes associated with brain colonization, we conducted microarray analysis and found that these two cell lines shared 138 gene expression patterns. Moreover, some of these genes were correlated with poor prognosis in HER2-positive breast cancer patients. Our findings might be helpful for further studying brain metastasis in HER2-positive breast cancer.
46
Singer, C. F., D. Gschwantler-Kaulich, A. Fink-Retter, G. Hudelist, C. Haas, K. Czerwenka, E. Kubista, and E. Kubista. "Differential gene expression profile in breast cancer-derived stromal fibroblasts." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 21075. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.21075.
Full textAbstract:
21075 Background: Breast cancer is chatacterized by malignant transformation of epithelial cells, but stromal cells also play an important role in tumorigenesis. While tumoral fibroblasts display unique phenotypical properties, it is unclear whether they also represent are a specific subpopulation. Materials and Methods: Stromal fibroblasts deriving from malignant tissue of 10 women with invasive breast cancer, and from normal breast tissue of 10 women with benign breast disorders, were subjected to differential complementary DNA Microarray Analysis by using a 2400 gene cDNA array. Gene expression results were validated by real-time PCR and by immunohistochemistry. Results: In a cDNA Array that allows to analyze the differential gene expression of more than 2400 genes, the mRNA expression of 135 genes were increased more than 2 fold in fibroblasts from malignant breast tumors. The majority of these genes encode tumor-promoting cytokines, transcription factors and cell-matrix associated proteins. The mRNA expression of 110 genes decreased to less than 0.5 fold. The remaining 2155 genes were not significantly altered. Immunohistochemistry for selected proteins performed on biopsies from breast cancer and normal breast tissues confirmed the clinical relevance of our findings. Conclusion: Breast cancer-derived stromal fibroblasts show a distinctive gene expression pattern that differentiates them from normal breast stroma. Our observation of increased expression of tumor promotion-associated genes even in the absence of adjacent malignant epithelium suggests that tumor stroma is comprised of a fibroblastic subpopulation that provides for a microenvironment which supports tumor growth and invasion. No significant financial relationships to disclose.
47
Desestret, V., D. Pissaloux, I. Treilleux, M. Small, M. Robert, V. Rogemond, G. Picard, D. Psimaras, A. Alentorn, and J. Honnorat. "JS1.1 Specific genetic alterations of breast tumors lead to Yo paraneoplastic cerebellar syndromes." Neuro-Oncology 21, Supplement_3 (August 2019): iii4. http://dx.doi.org/10.1093/neuonc/noz126.010.
Full textAbstract:
Abstract BACKGROUND Paraneoplastic cerebellar degenerations with anti-Yo antibodies (Yo-PCD) are rare syndromes associated with ovarian or breast cancers and caused by an auto-immune response against neuronal antigens expressed by tumor cells. We previously demonstrated in Yo-PCD ovarian cancers an association between massive infiltration of ovarian tumors by activated immune effector cells and recurrent gains and/or mutations of onconeural Yo genes (CDR2L and CDR2), suggesting that such genetic alterations in ovarian tumor cells may trigger immune tolerance breakdown and initiation of the auto-immune reaction against Purkinje cells. MATERIAL AND METHODS We pursued the characterization of Yo-PCD tumors and specifically studied breast cancer by IHC, FISH, CGH array and RNA sequencing analysis of 17 breast Yo-PCD tumors and by comparing their genetic characteristics with 10 sporadic breast tumors and public databases. RESULTS We confirmed that specific genetic alterations were also present in breast cancers associated with Yo-PCD. Moreover, this study provides additional evidence for a role of tumor cell specificities in PCD immunopathology by revealing peculiarities in Yo-PCD breast tumors compared to Yo-PCD ovarian cancer. Indeed, not only the CDR2L Yo gene was amplified in 8/9 breast Yo-PCD cancers but also the Erb2/Her2 gene in 15/16 (both genes are on chromosome 17q). In addition to this original Her2 and Yo antigen amplification confirmed by FISH, we observed an overexpression of these proteins by IHC analysis. These Yo-PCD breast cancers are also all negative for hormone receptors (HR). Thus, Yo-PCD breast tumors seem to belong to the molecularly and clinically distinct class of HR-negative and Her2-enriched breast cancers, which represents less than 10 % of breast cancers in the general population. Transcriptomic analysis confirmed that breast Yo-PCD tumors differ by their expression programs from classical breast cancers molecular subtypes. CONCLUSION Understanding the tumor genetic features leading to the immune breakdown and anti-tumor immune response as well as nervous tissue attack remains challenging and seems to be specific according to the tumor subtypes. Herein, our results suggest that, despite sharing common genetic alterations (copy number variations and mutations affecting Yo genes), the Yo-PCD immunopathogenesis of breast and ovarian cancers differ by involving different tumor-specific molecular pathways.
48
Ansari, Narges, Saeid Shahrabi, Abbas Khosravi, Reza Shirzad, and Hadi Rezaeean. "Prognostic Significance of CHEK2 Mutation in Progression of Breast Cancer." Laboratory Medicine 50, no. 3 (April 11, 2019): e36-e41. http://dx.doi.org/10.1093/labmed/lmz009.
Full textAbstract:
Abstract Breast cancer (BC) is one of the most common cancers among women; genetic mutations reflect the development of this disease. Mutations in cell signaling factors can be the main cause of BC development. In this study, we focused on mutations in checkpoint kinase 2 (CHEK2) and their impact as a prognostic factor in the pathogenesis of BC. CHEK2 is controlled in cell signaling pathways through the influence of upstream genes. Also, several downstream genes are regulated by CHEK2. In addition, mutations in CHEK2 lead to resistance of BC cells to chemotherapy and metastasis of cancer cells to other parts of the body. Finally, detection of mutations in CHEK2 can be used as a prognostic factor for patient response to treatment and for targeting downstream molecules of CHEK2 that are involved in the proliferation of breast tumor cells. Mutations such as c.1100delC and I157T can distinguish which patients are susceptible to metastasis.
49
Chen, Yu-Chih, Saswat Sahoo, Riley Brien, Seungwon Jung, Brock Humphries, Woncheol Lee, Yu-Heng Cheng, et al. "Single-cell RNA-sequencing of migratory breast cancer cells: discovering genes associated with cancer metastasis." Analyst 144, no. 24 (2019): 7296–309. http://dx.doi.org/10.1039/c9an01358j.
Full textAbstract:
We enriched migratory breast cancer cells with enhanced tumor formation and metastasis capability using microfluidics and performed single-cell RNA-sequencing to identify unique EMT and CSC signature of migratory cells.
50
Bozgeyik, Esra. "MicroRNA-17-5p targets expression of cancer-associated genes in breast cancer cells." Meta Gene 24 (June 2020): 100614. http://dx.doi.org/10.1016/j.mgene.2019.100614.
Full text