To see the other types of publications on this topic, follow the link: C-myc gene.
Journal articles on the topic 'C-myc gene'
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 'C-myc gene.'
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
Zobel, Andrea, Frank Kalkbrenner, Gerd Vorbrueggen, and Karin Moelling. "Transactivation of the human c-myc gene by c-Myb." Biochemical and Biophysical Research Communications 186, no. 2 (July 1992): 715–22. http://dx.doi.org/10.1016/0006-291x(92)90805-u.
Full text
2
Evans, J. L., T. L. Moore, W. M. Kuehl, T. Bender, and J. P. Ting. "Functional analysis of c-Myb protein in T-lymphocytic cell lines shows that it trans-activates the c-myc promoter." Molecular and Cellular Biology 10, no. 11 (November 1990): 5747–52. http://dx.doi.org/10.1128/mcb.10.11.5747.
Full textAbstract:
The function of c-Myb protein was revealed by transfecting an expression vector containing the entire c-Myb protein-coding sequence into the murine CTLL-2 T-cell line. Expressions of high levels of c-Myb protein did not alter the expression of several T-cell markers, c-fos mRNA expression, responses to interleukin-2, and growth characteristics of these cells. Interestingly, expression of the c-myc gene was drastically increased in this clone. Further, the c-myb expression plasmid, but not a frameshift mutant of c-myb, enhanced the expression of a hybrid construct of c-myc promoter linked to a reporter gene by 8- to 14-fold. These results demonstrate a role of c-Myb protein in c-myc gene expression.
3
Evans, J. L., T. L. Moore, W. M. Kuehl, T. Bender, and J. P. Ting. "Functional analysis of c-Myb protein in T-lymphocytic cell lines shows that it trans-activates the c-myc promoter." Molecular and Cellular Biology 10, no. 11 (November 1990): 5747–52. http://dx.doi.org/10.1128/mcb.10.11.5747-5752.1990.
Full textAbstract:
The function of c-Myb protein was revealed by transfecting an expression vector containing the entire c-Myb protein-coding sequence into the murine CTLL-2 T-cell line. Expressions of high levels of c-Myb protein did not alter the expression of several T-cell markers, c-fos mRNA expression, responses to interleukin-2, and growth characteristics of these cells. Interestingly, expression of the c-myc gene was drastically increased in this clone. Further, the c-myb expression plasmid, but not a frameshift mutant of c-myb, enhanced the expression of a hybrid construct of c-myc promoter linked to a reporter gene by 8- to 14-fold. These results demonstrate a role of c-Myb protein in c-myc gene expression.
4
Cogswell, J. P., P. C. Cogswell, W. M. Kuehl, A. M. Cuddihy, T. M. Bender, U. Engelke, K. B. Marcu, and J. P. Ting. "Mechanism of c-myc regulation by c-Myb in different cell lineages." Molecular and Cellular Biology 13, no. 5 (May 1993): 2858–69. http://dx.doi.org/10.1128/mcb.13.5.2858.
Full textAbstract:
Activation of the murine c-myc promoter by murine c-Myb protein was examined in several cell lines by using a transient expression system in which Myb expression vectors activate the c-myc promoter linked to a chloramphenicol acetyltransferase reporter gene or a genomic beta-globin gene. S1 nuclease protection analyses confirmed that the induction of c-myc by c-Myb was transcriptional and affected both P1 and P2 start sites in a murine T-cell line, EL4, and a myelomonocytic line, WEHI-3. Mutational analyses of the c-myc promoter revealed that two distinct regions could confer Myb responsiveness in two T-cell lines, a distal site upstream of P1 and a proximal site within the first noncoding exon. In contrast, only the proximal site was required for other cell lineages examined. Five separate Myb-binding sites were located in this proximal site and found to be important for c-Myb trans activation. DNA binding was necessary for c-myc activation, as shown by the loss of function associated with mutation of Myb's DNA-binding domain and by trans-dominant repressor activity of the DNA binding, trans-activation-defective mutant. The involvement of additional protein factors was addressed by inhibiting protein synthesis with cycloheximide in a conditional expression system in which the activity of presynthesized Myb was under the control of estrogen. These experiments indicate that de novo synthesis of additional proteins was not necessary for c-myc trans activation. Together these data reveal two cell lineage-dependent pathways by which c-Myb regulates c-myc; however, both pathways are mechanistically indistinguishable in that direct DNA binding by Myb is required for activating c-myc whereas neither de novo protein synthesis nor other labile proteins are necessary.
5
Cogswell, J. P., P. C. Cogswell, W. M. Kuehl, A. M. Cuddihy, T. M. Bender, U. Engelke, K. B. Marcu, and J. P. Ting. "Mechanism of c-myc regulation by c-Myb in different cell lineages." Molecular and Cellular Biology 13, no. 5 (May 1993): 2858–69. http://dx.doi.org/10.1128/mcb.13.5.2858-2869.1993.
Full textAbstract:
Activation of the murine c-myc promoter by murine c-Myb protein was examined in several cell lines by using a transient expression system in which Myb expression vectors activate the c-myc promoter linked to a chloramphenicol acetyltransferase reporter gene or a genomic beta-globin gene. S1 nuclease protection analyses confirmed that the induction of c-myc by c-Myb was transcriptional and affected both P1 and P2 start sites in a murine T-cell line, EL4, and a myelomonocytic line, WEHI-3. Mutational analyses of the c-myc promoter revealed that two distinct regions could confer Myb responsiveness in two T-cell lines, a distal site upstream of P1 and a proximal site within the first noncoding exon. In contrast, only the proximal site was required for other cell lineages examined. Five separate Myb-binding sites were located in this proximal site and found to be important for c-Myb trans activation. DNA binding was necessary for c-myc activation, as shown by the loss of function associated with mutation of Myb's DNA-binding domain and by trans-dominant repressor activity of the DNA binding, trans-activation-defective mutant. The involvement of additional protein factors was addressed by inhibiting protein synthesis with cycloheximide in a conditional expression system in which the activity of presynthesized Myb was under the control of estrogen. These experiments indicate that de novo synthesis of additional proteins was not necessary for c-myc trans activation. Together these data reveal two cell lineage-dependent pathways by which c-Myb regulates c-myc; however, both pathways are mechanistically indistinguishable in that direct DNA binding by Myb is required for activating c-myc whereas neither de novo protein synthesis nor other labile proteins are necessary.
6
Arsura, Marcello, Claudia S. Hofmann, Josee Golay, Martino Introna, and Gail E. Sonenshein. "A-myb rescues murine B-cell lymphomas from IgM-receptor–mediated apoptosis through c-myctranscriptional regulation." Blood 96, no. 3 (August 1, 2000): 1013–20. http://dx.doi.org/10.1182/blood.v96.3.1013.
Full textAbstract:
Abstract A-myb is a member of the myb family of transcription factors, which regulates proliferation, differentiation, and apoptosis of hematopoietic cells. A-Myb expression is normally restricted to the proliferating B-cell centroblasts and transgenic mice overexpressing A-myb displayed enhanced hyperplasia of the lymph nodes. Because A-Myb is highly expressed in several subtypes of human B-cell neoplasias, we sought to determine whether the A-myb gene promoted proliferation and survival of B lymphocytes, using the WEHI 231 and CH33 murine B-cell lymphomas as models. Here, we show that ectopic expression of A-mybrescues WEHI 231 and CH33 cells from growth arrest and apoptosis induced by anti-IgM treatment. Previously, we demonstrated an essential role of the c-myc gene in promoting cell survival of WEHI 231 cells in response to a variety of apoptotic stimuli. Furthermore, we and others have shown that the c-myc gene is potently transactivated by A-Myb in several cell types. Thus, we sought to determine whether c-Myc would mediate the A-Myb antiapoptotic effect in B cells. Here we show that ectopic expression of A-myb leads to maintenance of c-myc expression, and that expression of antisense c-myc RNA ablates A-Myb–mediated survival signals. Thus, these findings strongly implicate the A-myb gene in the regulation of B-cell survival and confirm the c-myc gene as one of the downstream targets of A-myb in these cells. Overall, our observation suggests that A-mybexpression may be relevant to the pathology of human B-cell neoplasias.
7
Arsura, Marcello, Claudia S. Hofmann, Josee Golay, Martino Introna, and Gail E. Sonenshein. "A-myb rescues murine B-cell lymphomas from IgM-receptor–mediated apoptosis through c-myctranscriptional regulation." Blood 96, no. 3 (August 1, 2000): 1013–20. http://dx.doi.org/10.1182/blood.v96.3.1013.015k06_1013_1020.
Full textAbstract:
A-myb is a member of the myb family of transcription factors, which regulates proliferation, differentiation, and apoptosis of hematopoietic cells. A-Myb expression is normally restricted to the proliferating B-cell centroblasts and transgenic mice overexpressing A-myb displayed enhanced hyperplasia of the lymph nodes. Because A-Myb is highly expressed in several subtypes of human B-cell neoplasias, we sought to determine whether the A-myb gene promoted proliferation and survival of B lymphocytes, using the WEHI 231 and CH33 murine B-cell lymphomas as models. Here, we show that ectopic expression of A-mybrescues WEHI 231 and CH33 cells from growth arrest and apoptosis induced by anti-IgM treatment. Previously, we demonstrated an essential role of the c-myc gene in promoting cell survival of WEHI 231 cells in response to a variety of apoptotic stimuli. Furthermore, we and others have shown that the c-myc gene is potently transactivated by A-Myb in several cell types. Thus, we sought to determine whether c-Myc would mediate the A-Myb antiapoptotic effect in B cells. Here we show that ectopic expression of A-myb leads to maintenance of c-myc expression, and that expression of antisense c-myc RNA ablates A-Myb–mediated survival signals. Thus, these findings strongly implicate the A-myb gene in the regulation of B-cell survival and confirm the c-myc gene as one of the downstream targets of A-myb in these cells. Overall, our observation suggests that A-mybexpression may be relevant to the pathology of human B-cell neoplasias.
8
Woloschak, M., J. L. Roberts, and K. Post. "c-myc, c-fos, and c-myb gene expression in human pituitary adenomas." Journal of Clinical Endocrinology & Metabolism 79, no. 1 (July 1994): 253–57. http://dx.doi.org/10.1210/jcem.79.1.8027238.
Full text
9
Woloschak, M. "c-myc, c-fos, and c-myb gene expression in human pituitary adenomas." Journal of Clinical Endocrinology & Metabolism 79, no. 1 (July 1, 1994): 253–57. http://dx.doi.org/10.1210/jc.79.1.253.
Full text
10
Mestdagh, P., E. Fredlund, F. Pattyn, J. H. Schulte, D. Muth, J. Vermeulen, C. Kumps, et al. "MYCN/c-MYC-induced microRNAs repress coding gene networks associated with poor outcome in MYCN/c-MYC-activated tumors." Oncogene 29, no. 9 (November 30, 2009): 1394–404. http://dx.doi.org/10.1038/onc.2009.429.
Full text
11
Hoffman-Liebermann, B., and D. A. Liebermann. "Interleukin-6- and leukemia inhibitory factor-induced terminal differentiation of myeloid leukemia cells is blocked at an intermediate stage by constitutive c-myc." Molecular and Cellular Biology 11, no. 5 (May 1991): 2375–81. http://dx.doi.org/10.1128/mcb.11.5.2375.
Full textAbstract:
Interleukin-6 (IL-6) and leukemia inhibitory factor (LIF), two multifunctional cytokines, recently have been identified as physiological inducers of hematopoietic cell differentiation which also induce terminal differentiation and growth arrest of the myeloblastic leukemic M1 cell line. In this work, it is shown that c-myc exhibited a unique pattern of expression upon induction of M1 terminal differentiation by LIF or IL-6, with an early transient increase followed by a decrease to control levels by 12 h and no detectable c-myc mRNA by 1 day; in contrast, c-myb expression was rapidly suppressed, with no detectable c-myb mRNA by 12 h. Vectors containing the c-myc gene under control of the beta-actin gene promoter were transfected into M1 cells to obtain M1myc cell lines which constitutively synthesized c-myc. Deregulated and continued expression of c-myc blocked terminal differentiation induced by IL-6 or LIF at an intermediate stage in the progression from immature blasts to mature macrophages, precisely at the point in time when c-myc is normally suppressed, leading to intermediate-stage myeloid cells which continued to proliferate in the absence of c-myb expression.
12
Hoffman-Liebermann, B., and D. A. Liebermann. "Interleukin-6- and leukemia inhibitory factor-induced terminal differentiation of myeloid leukemia cells is blocked at an intermediate stage by constitutive c-myc." Molecular and Cellular Biology 11, no. 5 (May 1991): 2375–81. http://dx.doi.org/10.1128/mcb.11.5.2375-2381.1991.
Full textAbstract:
Interleukin-6 (IL-6) and leukemia inhibitory factor (LIF), two multifunctional cytokines, recently have been identified as physiological inducers of hematopoietic cell differentiation which also induce terminal differentiation and growth arrest of the myeloblastic leukemic M1 cell line. In this work, it is shown that c-myc exhibited a unique pattern of expression upon induction of M1 terminal differentiation by LIF or IL-6, with an early transient increase followed by a decrease to control levels by 12 h and no detectable c-myc mRNA by 1 day; in contrast, c-myb expression was rapidly suppressed, with no detectable c-myb mRNA by 12 h. Vectors containing the c-myc gene under control of the beta-actin gene promoter were transfected into M1 cells to obtain M1myc cell lines which constitutively synthesized c-myc. Deregulated and continued expression of c-myc blocked terminal differentiation induced by IL-6 or LIF at an intermediate stage in the progression from immature blasts to mature macrophages, precisely at the point in time when c-myc is normally suppressed, leading to intermediate-stage myeloid cells which continued to proliferate in the absence of c-myb expression.
13
Dang, Chi V., Kathryn A. O’Donnell, Karen I. Zeller, Tam Nguyen, Rebecca C. Osthus, and Feng Li. "The c-Myc target gene network." Seminars in Cancer Biology 16, no. 4 (August 2006): 253–64. http://dx.doi.org/10.1016/j.semcancer.2006.07.014.
Full text
14
SKRZYPCZAK, MACIEJ, JULITA ZIELEWICZ, STANISŁAW WINIARCZYK, JACEK WOJCIEROWSKI, ANNA KWAŚNIEWSKA, and JERZY JAKOWICKI. "Expression of c-MYC gene in neoplastic endometrium." PRZEGLĄD GINEKOLOGICZNO-POŁOŻNICZY 5, no. 1-1 (February 23, 2005): 15–20. http://dx.doi.org/10.1066/s10014040059.
Full text
15
Batsché, Eric, and Chantal Crémisi. "Opposite transcriptional activity between the wild type c-myc gene coding for c-Myc1 and c-Myc2 proteins and c-Myc1 and c-Myc2 separately." Oncogene 18, no. 41 (October 1999): 5662–71. http://dx.doi.org/10.1038/sj.onc.1202927.
Full text
16
Schmidt, M., V. Nazarov, L. Stevens, R. Watson, and L. Wolff. "Regulation of the Resident Chromosomal Copy of c-myc by c-Myb Is Involved in Myeloid Leukemogenesis." Molecular and Cellular Biology 20, no. 6 (March 15, 2000): 1970–81. http://dx.doi.org/10.1128/mcb.20.6.1970-1981.2000.
Full textAbstract:
ABSTRACT c-myb is a frequent target of retroviral insertional mutagenesis in murine leukemia virus-induced myeloid leukemia. Induction of the leukemogenic phenotype is generally associated with inappropriate expression of this transcriptional regulator. Despite intensive investigations, the target genes of c-myb that are specifically involved in development of these myeloid lineage neoplasms are still unknown. In vitro assays have indicated that c-myc may be a target gene of c-Myb; however, regulation of the resident chromosomal gene has not yet been demonstrated. To address this question further, we analyzed the expression of c-mycin a myeloblastic cell line, M1, expressing a conditionally active c-Myb–estrogen receptor fusion protein (MybER). Activation of MybER both prevented the growth arrest induced by interleukin-6 (IL-6) and rapidly restored c-myc expression in nearly terminal differentiated cells that had been exposed to IL-6 for 3 days. Restoration occurred in the presence of a protein synthesis inhibitor but not after a transcriptional block, indicating that c-myc is a direct, transcriptionally regulated target of c-Myb. c-myc is a major target that transduces Myb's proliferative signal, as shown by the ability of a c-Myc–estrogen receptor fusion protein alone to also reverse growth arrest in this system. To investigate the possibility that this regulatory connection contributes to Myb's oncogenicity, we expressed a dominant negative Myb in the myeloid leukemic cell line RI-4-11. In this cell line, c-myb is activated by insertional mutagenesis and cannot be effectively down regulated by cytokine. Myb's ability to regulate c-myc's expression was also demonstrated in these cells, showing a mechanism through which the proto-oncogene c-mybcan exert its oncogenic potential in myeloid lineage hematopoietic cells.
17
Pallavicini, M. G., C. Rosette, M. Reitsma, P. S. Deteresa, and J. W. Gray. "Relationship of c-myc gene copy number and gene expression: Cellular effects of elevated c-myc protein." Journal of Cellular Physiology 143, no. 2 (May 1990): 372–80. http://dx.doi.org/10.1002/jcp.1041430223.
Full text
18
Mango, S. E., G. D. Schuler, M. E. Steele, and M. D. Cole. "Germ line c-myc is not down-regulated by loss or exclusion of activating factors in myc-induced macrophage tumors." Molecular and Cellular Biology 9, no. 8 (August 1989): 3482–90. http://dx.doi.org/10.1128/mcb.9.8.3482.
Full textAbstract:
As in tumors with c-myc chromosomal translocations, c-myc retrovirus-induced monocyte tumors constitutively express an activated form of c-myc (the proviral gene), whereas the normal endogenous c-myc genes are transcriptionally silent. Treatment of these retrovirus-induced tumor cells with a number of bioactive chemicals and growth factors that are known to induce c-myc expression in cells of the monocyte lineage failed to induce the endogenous c-myc gene. In contrast, the same treatments induced the c-fos gene in both tumors and a control macrophage line. To investigate c-myc suppression further, a normal copy of the human c-myc gene was introduced into tumor and control cell lines by using a retrovirus with self-inactivating long terminal repeats. This transduced normal gene was expressed at equivalent levels in all cells, regardless of the state of endogenous c-myc gene expression, and was strongly induced by agents that induce the normal gene in the control cells. These results indicate that the signal transduction pathways that normally activate the c-myc gene are functional in myc-induced tumor cells and suggest that endogenous c-myc is actively suppressed. An examination of the c-myc locus itself showed that the lack of transcriptional activity correlated with the absence of several prominent DNase I-hypersensitive sites in the 5'-flanking region of the gene but without loss of general DNase sensitivity. Furthermore, analysis of 22 methylation-sensitive restriction enzyme sites in the 5'-flanking region, first exon, and first intron indicated that the silent c-myc genes remained in the same unmethylated state as did actively expressed genes. Thus, c-myc suppression does not appear to result from the most frequently described mechanisms of gene inactivation.
19
Mango, S. E., G. D. Schuler, M. E. Steele, and M. D. Cole. "Germ line c-myc is not down-regulated by loss or exclusion of activating factors in myc-induced macrophage tumors." Molecular and Cellular Biology 9, no. 8 (August 1989): 3482–90. http://dx.doi.org/10.1128/mcb.9.8.3482-3490.1989.
Full textAbstract:
As in tumors with c-myc chromosomal translocations, c-myc retrovirus-induced monocyte tumors constitutively express an activated form of c-myc (the proviral gene), whereas the normal endogenous c-myc genes are transcriptionally silent. Treatment of these retrovirus-induced tumor cells with a number of bioactive chemicals and growth factors that are known to induce c-myc expression in cells of the monocyte lineage failed to induce the endogenous c-myc gene. In contrast, the same treatments induced the c-fos gene in both tumors and a control macrophage line. To investigate c-myc suppression further, a normal copy of the human c-myc gene was introduced into tumor and control cell lines by using a retrovirus with self-inactivating long terminal repeats. This transduced normal gene was expressed at equivalent levels in all cells, regardless of the state of endogenous c-myc gene expression, and was strongly induced by agents that induce the normal gene in the control cells. These results indicate that the signal transduction pathways that normally activate the c-myc gene are functional in myc-induced tumor cells and suggest that endogenous c-myc is actively suppressed. An examination of the c-myc locus itself showed that the lack of transcriptional activity correlated with the absence of several prominent DNase I-hypersensitive sites in the 5'-flanking region of the gene but without loss of general DNase sensitivity. Furthermore, analysis of 22 methylation-sensitive restriction enzyme sites in the 5'-flanking region, first exon, and first intron indicated that the silent c-myc genes remained in the same unmethylated state as did actively expressed genes. Thus, c-myc suppression does not appear to result from the most frequently described mechanisms of gene inactivation.
20
Coppola, J. A., J. M. Parker, G. D. Schuler, and M. D. Cole. "Continued withdrawal from the cell cycle and regulation of cellular genes in mouse erythroleukemia cells blocked in differentiation by the c-myc oncogene." Molecular and Cellular Biology 9, no. 4 (April 1989): 1714–20. http://dx.doi.org/10.1128/mcb.9.4.1714.
Full textAbstract:
Constitutive expression of the c-myc oncogene blocks dimethyl sulfoxide (DMSO)-induced differentiation of mouse erythroleukemia (MEL) cells. During the first 12 h of treatment with DMSO, MEL cells undergo a temporary decrease in the level of c-myc mRNA, followed by a temporary withdrawal from the cell cycle. We found the same shutoff of DNA synthesis during the first 12 to 30 h after DMSO induction in normal MEL cells (which differentiate) and in c-myc-transfected MEL cells (which do not differentiate). We also examined whether deregulated c-myc expression grossly interfered with the regulation of gene expression during MEL cell differentiation. We used run-on transcription assays to monitor the rate of transcription of four oncogenes (c-myc, c-myb, c-fos, and c-K-ras); all except c-K-ras showed a rapid but temporary decrease in transcription after induction in both c-myc-transfected and control cells. Finally, we found the same regulation of cytoplasmic mRNA expression in both types of cells for four oncogenes and three housekeeping genes associated with growth. We conclude that in the MEL cell system, the effects of deregulated c-myc expression do not occur through a disruption of cell cycle control early in induction, nor do they occur through gross deregulation of gene expression.
21
Coppola, J. A., J. M. Parker, G. D. Schuler, and M. D. Cole. "Continued withdrawal from the cell cycle and regulation of cellular genes in mouse erythroleukemia cells blocked in differentiation by the c-myc oncogene." Molecular and Cellular Biology 9, no. 4 (April 1989): 1714–20. http://dx.doi.org/10.1128/mcb.9.4.1714-1720.1989.
Full textAbstract:
Constitutive expression of the c-myc oncogene blocks dimethyl sulfoxide (DMSO)-induced differentiation of mouse erythroleukemia (MEL) cells. During the first 12 h of treatment with DMSO, MEL cells undergo a temporary decrease in the level of c-myc mRNA, followed by a temporary withdrawal from the cell cycle. We found the same shutoff of DNA synthesis during the first 12 to 30 h after DMSO induction in normal MEL cells (which differentiate) and in c-myc-transfected MEL cells (which do not differentiate). We also examined whether deregulated c-myc expression grossly interfered with the regulation of gene expression during MEL cell differentiation. We used run-on transcription assays to monitor the rate of transcription of four oncogenes (c-myc, c-myb, c-fos, and c-K-ras); all except c-K-ras showed a rapid but temporary decrease in transcription after induction in both c-myc-transfected and control cells. Finally, we found the same regulation of cytoplasmic mRNA expression in both types of cells for four oncogenes and three housekeeping genes associated with growth. We conclude that in the MEL cell system, the effects of deregulated c-myc expression do not occur through a disruption of cell cycle control early in induction, nor do they occur through gross deregulation of gene expression.
22
Small, M. B., N. Hay, M. Schwab, and J. M. Bishop. "Neoplastic transformation by the human gene N-myc." Molecular and Cellular Biology 7, no. 5 (May 1987): 1638–45. http://dx.doi.org/10.1128/mcb.7.5.1638.
Full textAbstract:
Amplification and abundant expression of a gene known as N-myc are found frequently in advanced stages of human neuroblastoma and may play a role in the genesis of several malignant human tumors. Previous studies have shown that N-myc can cooperate with a mutant allele of the proto-oncogene c-Ha-ras to transform embryonic rat cells in culture. Here we show that N-myc can also act alone to elicit neoplastic growth of an established line of rat fibroblasts (Rat-1). We used recombinant DNA vectors to express either N-myc or its kindred gene c-myc in transfected cells. Both genes caused morphological transformation, anchorage-independent growth, and tumorigenicity. We noticed two variables that appeared to influence the ability to isolate cells transformed by N-myc and c-myc: the abundance in which the genes were expressed and biological selection to eliminate untransformed cells from the cultures. Our findings sustain the belief that N-myc is an authentic proto-oncogene, lend further credibility to the role of N-myc in the genesis of human tumors, and establish a convenient assay that can be used to explore further the properties of both N-myc and c-myc.
23
Small, M. B., N. Hay, M. Schwab, and J. M. Bishop. "Neoplastic transformation by the human gene N-myc." Molecular and Cellular Biology 7, no. 5 (May 1987): 1638–45. http://dx.doi.org/10.1128/mcb.7.5.1638-1645.1987.
Full textAbstract:
Amplification and abundant expression of a gene known as N-myc are found frequently in advanced stages of human neuroblastoma and may play a role in the genesis of several malignant human tumors. Previous studies have shown that N-myc can cooperate with a mutant allele of the proto-oncogene c-Ha-ras to transform embryonic rat cells in culture. Here we show that N-myc can also act alone to elicit neoplastic growth of an established line of rat fibroblasts (Rat-1). We used recombinant DNA vectors to express either N-myc or its kindred gene c-myc in transfected cells. Both genes caused morphological transformation, anchorage-independent growth, and tumorigenicity. We noticed two variables that appeared to influence the ability to isolate cells transformed by N-myc and c-myc: the abundance in which the genes were expressed and biological selection to eliminate untransformed cells from the cultures. Our findings sustain the belief that N-myc is an authentic proto-oncogene, lend further credibility to the role of N-myc in the genesis of human tumors, and establish a convenient assay that can be used to explore further the properties of both N-myc and c-myc.
24
Gaubatz, S., A. Meichle, and M. Eilers. "An E-box element localized in the first intron mediates regulation of the prothymosin alpha gene by c-myc." Molecular and Cellular Biology 14, no. 6 (June 1994): 3853–62. http://dx.doi.org/10.1128/mcb.14.6.3853.
Full textAbstract:
In RAT1A fibroblasts, expression of the prothymosin alpha gene is under the transcriptional control of the c-myc proto-oncogene. We have now cloned the rat gene encoding prothymosin alpha and show that the cloned gene is regulated by c-myc in vivo. We find that regulation by c-myc is mediated by sequences downstream of the transcriptional start site, whereas the promoter is constitutive and not regulated by c-myc. We have identified an enhancer element within the first intron that is sufficient to mediate a response to Myc and Max in transient transfection assays and to activation of estrogen receptor-Myc chimeras in vivo. We find that this element contains a consensus Myc-binding site (CACGTG). Disruption of this site abolishes the response to Myc and Max in both transient and stable assays. Mutants of either Myc or Max that are deficient for heterodimerization fail to regulate the prothymosin alpha gene, suggesting that a heterodimer between Myc and Max activates the prothymosin alpha gene. Our data define the prothymosin alpha gene as a bona fide target gene for c-myc.
25
Gaubatz, S., A. Meichle, and M. Eilers. "An E-box element localized in the first intron mediates regulation of the prothymosin alpha gene by c-myc." Molecular and Cellular Biology 14, no. 6 (June 1994): 3853–62. http://dx.doi.org/10.1128/mcb.14.6.3853-3862.1994.
Full textAbstract:
In RAT1A fibroblasts, expression of the prothymosin alpha gene is under the transcriptional control of the c-myc proto-oncogene. We have now cloned the rat gene encoding prothymosin alpha and show that the cloned gene is regulated by c-myc in vivo. We find that regulation by c-myc is mediated by sequences downstream of the transcriptional start site, whereas the promoter is constitutive and not regulated by c-myc. We have identified an enhancer element within the first intron that is sufficient to mediate a response to Myc and Max in transient transfection assays and to activation of estrogen receptor-Myc chimeras in vivo. We find that this element contains a consensus Myc-binding site (CACGTG). Disruption of this site abolishes the response to Myc and Max in both transient and stable assays. Mutants of either Myc or Max that are deficient for heterodimerization fail to regulate the prothymosin alpha gene, suggesting that a heterodimer between Myc and Max activates the prothymosin alpha gene. Our data define the prothymosin alpha gene as a bona fide target gene for c-myc.
26
Palkó, Enikő, Szilárd Póliska, Zsuzsanna Csákányi, Gábor Katona, Tamás Karosi, Frigyes Helfferich, András Penyige, and István Sziklai. "The c-MYC Protooncogene Expression in Cholesteatoma." BioMed Research International 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/639896.
Full textAbstract:
Cholesteatoma is an epidermoid cyst, which is most frequently found in the middle ear. The matrix of cholesteatoma is histologically similar to the matrix of the epidermoid cyst of the skin (atheroma); their epithelium is characterized by hyperproliferation. The c-MYC protooncogene located on chromosome 8q24 encodes a transcription factor involved in the regulation of cell proliferation and differentiation. Previous studies have found aneuploidy of chromosome 8, copy number variation of c-MYC gene, and the presence of elevated level c-MYC protein in cholesteatoma. In this study we have compared the expression of c-MYC gene in samples taken from the matrix of 26 acquired cholesteatomas (15 children and 11 adults), 15 epidermoid cysts of the skin (atheromas; head and neck region) and 5 normal skin samples (retroauricular region) using RT-qPCR, providing the first precise measurement of the expression of c-MYC gene in cholesteatoma. We have found significantly elevated c-MYC gene expression in cholesteatoma compared to atheroma and to normal skin samples. There was no significant difference, however, in c-MYC gene expression between cholesteatoma samples of children and adults. The significant difference in c-MYC gene expression level in cholesteatoma compared to that of atheroma implies a more prominent hyperproliferative phenotype which may explain the clinical behavior typical of cholesteatoma.
27
Prendergast, G. C., and M. D. Cole. "Posttranscriptional regulation of cellular gene expression by the c-myc oncogene." Molecular and Cellular Biology 9, no. 1 (January 1989): 124–34. http://dx.doi.org/10.1128/mcb.9.1.124.
Full textAbstract:
The c-myc oncogene has been implicated in the development of many different cancers, yet the mechanism by which the c-myc protein alters cellular growth control has proven elusive. We used a cDNA hybridization difference assay to isolate two genes, mr1 and mr2, that were constitutively expressed (i.e., deregulated) in rodent fibroblast cell lines immortalized by transfection of a viral promoter-linked c-myc gene. Both cDNAs were serum inducible in quiescent G0 fibroblasts, suggesting that they are functionally related to cellular proliferative processes. Although there were significant differences in cytoplasmic mRNA levels between myc-immortalized and control cells, the rates of transcription and mRNA turnover of both genes were similar, suggesting that c-myc regulates mr1 and mr2 expression by some nuclear posttranscriptional mechanism. mr1 was also rapidly (within 2 h) and specifically induced by dexamethasone in BALB/c cell lines expressing a mouse mammary tumor virus long terminal repeat-driven myc gene, under conditions where other growth factor-inducible genes were unaffected. A frameshift mutation in the mouse mammary tumor virus myc gene destroyed the dexamethasone stimulation of mr1, indicating that c-myc protein is required for the effect. As in the myc-immortalized cells, the induction of mr1 by c-myc occurred without detectable changes in mr1 transcription or cytoplasmic mRNA stability, implicating regulation, either direct or indirect, through a nuclear posttranscriptional mechanism. These results provide evidence that c-myc can rapidly modulate cellular gene expression and suggest that c-myc may function in gene regulation at the level of RNA export, splicing, or nuclear RNA turnover.
28
Prendergast, G. C., and M. D. Cole. "Posttranscriptional regulation of cellular gene expression by the c-myc oncogene." Molecular and Cellular Biology 9, no. 1 (January 1989): 124–34. http://dx.doi.org/10.1128/mcb.9.1.124-134.1989.
Full textAbstract:
The c-myc oncogene has been implicated in the development of many different cancers, yet the mechanism by which the c-myc protein alters cellular growth control has proven elusive. We used a cDNA hybridization difference assay to isolate two genes, mr1 and mr2, that were constitutively expressed (i.e., deregulated) in rodent fibroblast cell lines immortalized by transfection of a viral promoter-linked c-myc gene. Both cDNAs were serum inducible in quiescent G0 fibroblasts, suggesting that they are functionally related to cellular proliferative processes. Although there were significant differences in cytoplasmic mRNA levels between myc-immortalized and control cells, the rates of transcription and mRNA turnover of both genes were similar, suggesting that c-myc regulates mr1 and mr2 expression by some nuclear posttranscriptional mechanism. mr1 was also rapidly (within 2 h) and specifically induced by dexamethasone in BALB/c cell lines expressing a mouse mammary tumor virus long terminal repeat-driven myc gene, under conditions where other growth factor-inducible genes were unaffected. A frameshift mutation in the mouse mammary tumor virus myc gene destroyed the dexamethasone stimulation of mr1, indicating that c-myc protein is required for the effect. As in the myc-immortalized cells, the induction of mr1 by c-myc occurred without detectable changes in mr1 transcription or cytoplasmic mRNA stability, implicating regulation, either direct or indirect, through a nuclear posttranscriptional mechanism. These results provide evidence that c-myc can rapidly modulate cellular gene expression and suggest that c-myc may function in gene regulation at the level of RNA export, splicing, or nuclear RNA turnover.
29
Shiu, R. P., P. H. Watson, and D. Dubik. "c-myc oncogene expression in estrogen-dependent and -independent breast cancer." Clinical Chemistry 39, no. 2 (February 1, 1993): 353–55. http://dx.doi.org/10.1093/clinchem/39.2.353.
Full textAbstract:
Abstract We demonstrate that c-myc gene expression is essential for growth of breast cancer cells. It also plays an important role in the progression of human breast cancer. c-myc gene amplification may be important for cancer cell invasion, but perhaps not essential for nodal metastasis. We also provide compelling evidence that the c-myc oncogene is an estrogen target gene in hormone-responsive breast cancer. Hormonal progression of breast cancer could be brought about by the enhanced expression of the c-myc gene, with gene amplification and enhanced c-myc mRNA stability being two major mechanisms involved.
30
Liu, J., R. Voutilainen, A. I. Kahri, and P. Heikkilä. "Expression patterns of the c-myc gene in adrenocortical tumors and pheochromocytomas." Journal of Endocrinology 152, no. 2 (February 1997): 175–81. http://dx.doi.org/10.1677/joe.0.1520175.
Full textAbstract:
Abstract Abundant c-myc gene expression in neoplasms has been often linked to poor prognosis. As c-myc mRNA is expressed and hormonally regulated in human adrenals, we examined the c-myc gene expression in adrenal tumors by RNA analysis and immunohistochemistry to find out the possible role of c-myc in adrenal neoplasms. The abundant expression of the c-myc gene in normal adrenals was localized to the zona fasciculata and zona reticularis, with much lower expression in the zona glomerulosa and adrenal medulla. In hormonally active adrenocortical carcinomas (n=6) and in virilizing adenomas (n=4), c-myc mRNA levels were approximately 10% of those in normal adrenals (n=11). In contrast, adrenal adenomas from patients with Cushing's (n=4) and Conn's (n=9) syndrome, non-functional adenomas (n=2), adrenocortical hyperplasias (bilateral, n=5; nodular, n=4), and non-functional adrenocortical carcinomas (n=3) expressed c-myc mRNA to the same extent as normal adrenals. The c-myc mRNA abundance in benign adrenal pheochromocytomas (n=19) was similar to that in normal adrenal medulla. However, in malignant adrenal pheochromocytomas (n=6), the average c-myc mRNA levels were approximately threefold that in benign adrenal pheochromocytomas. There was a good correlation between c-myc mRNA expression and immunohistochemical reactivity in both normal and pathological adrenal tissues. Southern blot analysis revealed no amplification or rearrangement of the c-myc gene in any of the adrenal tumors. In conclusion, c-myc expression localized to zona fasciculata and reticularis in normal adrenals. Virilizing adenomas and hormonally active adrenocortical carcinomas expressed c-myc mRNA clearly less than the other adrenal neoplasms and normal adrenal tissue. On the other hand, malignant pheochromocytomas contained more c-myc mRNA than benign ones. Further studies are required to clarify the mechanisms and significance for the distinct expression pattern of the c-myc gene in different adrenal neoplasms. Journal of Endocrinology (1997) 152, 175–181
31
Yang, B. S., T. J. Geddes, R. J. Pogulis, B. de Crombrugghe, and S. O. Freytag. "Transcriptional suppression of cellular gene expression by c-Myc." Molecular and Cellular Biology 11, no. 4 (April 1991): 2291–95. http://dx.doi.org/10.1128/mcb.11.4.2291.
Full textAbstract:
High levels of c-Myc in mouse 3T3-L1 cells specifically suppress the expression of three collagen genes. This effect is exerted through collagen promoter sequences and requires the leucine zipper motif of c-Myc. Our data suggest that an important aspect of c-Myc transforming activity is the ability to suppress specific cellular gene transcription.
32
Yang, B. S., T. J. Geddes, R. J. Pogulis, B. de Crombrugghe, and S. O. Freytag. "Transcriptional suppression of cellular gene expression by c-Myc." Molecular and Cellular Biology 11, no. 4 (April 1991): 2291–95. http://dx.doi.org/10.1128/mcb.11.4.2291-2295.1991.
Full textAbstract:
High levels of c-Myc in mouse 3T3-L1 cells specifically suppress the expression of three collagen genes. This effect is exerted through collagen promoter sequences and requires the leucine zipper motif of c-Myc. Our data suggest that an important aspect of c-Myc transforming activity is the ability to suppress specific cellular gene transcription.
33
Resar, L. M., C. Dolde, J. F. Barrett, and C. V. Dang. "B-myc inhibits neoplastic transformation and transcriptional activation by c-myc." Molecular and Cellular Biology 13, no. 2 (February 1993): 1130–36. http://dx.doi.org/10.1128/mcb.13.2.1130.
Full textAbstract:
B-myc is a recently described myc gene whose product has not been functionally characterized. The predicted product of B-myc is a 168-amino-acid protein with extensive homology to the c-Myc amino-terminal region, previously shown to contain a transcriptional activation domain. We hypothesized that B-Myc might also function in transcriptional regulation, although its role in regulating gene expression is predicted to be unique, because B-Myc lacks the specific DNA-binding motif found in other Myc proteins. To determine whether B-Myc could interact with the transcriptional machinery, we studied the transcriptional activation properties of a chimeric protein containing B-Myc sequences fused to the DNA-binding domain of the yeast transcriptional activator GAL4 (GAL4-B-Myc). We found that GAL4-B-Myc strongly activated expression of a GAL4-regulated reporter gene in mammalian cells. In addition, full-length B-Myc was able to inhibit or squelch reporter gene activation by a GAL4 chimeric protein containing the c-Myc transcriptional activation domain. We also observed that B-Myc dramatically inhibited the neoplastic cotransforming activity of c-Myc and activated Ras in rat embryo cells. Because B-Myc inhibits both neoplastic transformation and transcriptional activation by c-Myc, we suggest that the transforming activity of c-Myc is related to its ability to regulate transcription. Whether B-Myc functions biologically to squelch transcription and/or to regulate transcription through a specific DNA-binding protein remains unestablished.
34
Resar, L. M., C. Dolde, J. F. Barrett, and C. V. Dang. "B-myc inhibits neoplastic transformation and transcriptional activation by c-myc." Molecular and Cellular Biology 13, no. 2 (February 1993): 1130–36. http://dx.doi.org/10.1128/mcb.13.2.1130-1136.1993.
Full textAbstract:
B-myc is a recently described myc gene whose product has not been functionally characterized. The predicted product of B-myc is a 168-amino-acid protein with extensive homology to the c-Myc amino-terminal region, previously shown to contain a transcriptional activation domain. We hypothesized that B-Myc might also function in transcriptional regulation, although its role in regulating gene expression is predicted to be unique, because B-Myc lacks the specific DNA-binding motif found in other Myc proteins. To determine whether B-Myc could interact with the transcriptional machinery, we studied the transcriptional activation properties of a chimeric protein containing B-Myc sequences fused to the DNA-binding domain of the yeast transcriptional activator GAL4 (GAL4-B-Myc). We found that GAL4-B-Myc strongly activated expression of a GAL4-regulated reporter gene in mammalian cells. In addition, full-length B-Myc was able to inhibit or squelch reporter gene activation by a GAL4 chimeric protein containing the c-Myc transcriptional activation domain. We also observed that B-Myc dramatically inhibited the neoplastic cotransforming activity of c-Myc and activated Ras in rat embryo cells. Because B-Myc inhibits both neoplastic transformation and transcriptional activation by c-Myc, we suggest that the transforming activity of c-Myc is related to its ability to regulate transcription. Whether B-Myc functions biologically to squelch transcription and/or to regulate transcription through a specific DNA-binding protein remains unestablished.
35
Wang, Jinghong, and Linda M. Boxer. "The Role of p53 in C-myc Induced Lymphomagenesis Mediated by the IgH 3′ Enhancers." Blood 106, no. 11 (November 16, 2005): 2610. http://dx.doi.org/10.1182/blood.v106.11.2610.2610.
Full textAbstract:
Abstract Translocation of the c-myc oncogene to the immunoglobulin heavy chain gene (IgH) locus is the most common chromosomal abnormality in Burkitt’s lymphoma. Our mouse model (IgH-3′E-myc) with the IgH 3′ enhancers integrated 5′ of the c-myc gene demonstrated that the IgH 3′ enhancers play an important role in c-myc deregulation and B cell lymphomagenesis. In this study, we examined the role of the tumor suppressor p53 in c-myc-induced B cell lymphomagenesis by developing IgH-3′E-myc mice with only a single p53 allele (p53+/−-mycE mice). We found that lymphoma development and death were significantly accelerated in these mice compared to the IgH-3′E-myc mice. p53+/−-mycE mice developed Burkitt-like B cell lymphomas at about 5 months of age, and the lymphomas had a clonal origin. In premalignant B cells, p53 expression was comparable to that in wildtype B cells; however, significantly decreased p53 levels were observed in malignant lymphoma cells. In addition, p53 expression was not up-regulated in response to etoposide in lymphoma cells. The remaining p53 allele was present, and no mutations were detected in the coding region. Increased expression of Mdm2 was observed in half of the lymphomas. Premalignant B cells from p53+/−-mycE mice showed higher induced and spontaneous apoptosis due to increased c-myc expression. However, malignant lymphoma cells had a greatly increased survival rate in culture and were more resistant to chemotherapeutic agents. The majority of the lymphomas showed increased expression of the anti-apoptotic protein Bcl-xL. We found that p53 could negatively regulate the bcl-xL promoter in lymphoma cells, and a region that was responsive to p53 in the bcl-xL promoter was identified. These data support the conclusion that decreased p53 levels and overexpression of Bcl-xL play an important role in c-myc-induced lymphomagenesis mediated by IgH 3′ enhancers.
36
Stommel, John R., Gordon J. Lightbourn, Brenda S. Winkel, and Robert J. Griesbach. "Transcription Factor Families Regulate the Anthocyanin Biosynthetic Pathway in Capsicum annuum." Journal of the American Society for Horticultural Science 134, no. 2 (March 2009): 244–51. http://dx.doi.org/10.21273/jashs.134.2.244.
Full textAbstract:
Anthocyanin structural gene transcription requires the expression of at least one member of each of three transcription factor families: MYC, MYB, and WD40. These transcription factors form a complex that binds to structural gene promoters, thereby modulating gene expression. Capsicum annuum L. (pepper) displays a wide spectrum of tissue-specific anthocyanin pigmentation, making it a useful model for the study of anthocyanin accumulation. To determine the genetic basis for tissue-specific pigmentation, we used real-time polymerase chain reaction to evaluate the expression of anthocyanin biosynthetic (Chs, Dfr, and Ans) and regulatory (Myc, MybA , and Wd) genes in flower, fruit, and foliar tissue from pigmented and nonpigmented C. annuum genotypes. No differences were observed in expression of the Wd gene among these tissues. However, in all cases, biosynthetic gene transcript levels were significantly higher in anthocyanin-pigmented tissue than in nonpigmented tissues. MybA and Myc transcript levels were also substantially higher in anthocyanin-pigmented floral and fruit tissues. Our results demonstrate that differential expression of C. annuum MybA as well as Myc occurs coincident with anthocyanin accumulation in C. annuum flower and fruit tissues. In contrast to the situation in flowers and fruit, differential expression of MybA and Myc was not observed in foliar tissue, suggesting that different mechanisms contribute to the regulation of anthocyanin biosynthesis in different parts of the C. annuum plant. Cloning and sequencing of MybA genomic and cDNA clones revealed two introns of 249 and 441 bp between the R2R3 domains. Whereas the Myb R2R3 domains were conserved between C. annuum and Petunia ×hybrida Vilm., the sequence of the non-R2R3 domains was not conserved, with very little homology in these related Solanaceous species.
37
Erisman, M. D., P. G. Rothberg, R. E. Diehl, C. C. Morse, J. M. Spandorfer, and S. M. Astrin. "Deregulation of c-myc gene expression in human colon carcinoma is not accompanied by amplification or rearrangement of the gene." Molecular and Cellular Biology 5, no. 8 (August 1985): 1969–76. http://dx.doi.org/10.1128/mcb.5.8.1969.
Full textAbstract:
The structure and expression of the c-myc oncogene were examined in 29 primary human colon adenocarcinomas. Dot blot hybridization of total RNA showed that 21 tumors (72%) had considerably elevated expression of c-myc (5- to 40-fold) relative to normal colonic mucosa. These data were corroborated by Northern blots of polyadenylated RNA, which showed a 2.3-kilobase transcript. Southern analysis of the c-myc locus in these tumors indicated the absence of amplification or DNA rearrangement in a 35-kilobase region encompassing the gene. In a parallel study, elevated expression of c-myc without amplification or DNA rearrangement was also observed in three of six colon carcinoma cell lines examined; in addition, unlike a normal colon cell line control, these three cell lines exhibited constitutive, high-level expression of the gene during their growth in cultures. These results indicate that elevated expression of the c-myc oncogene occurs frequently in primary human colon carcinomas and that the mechanism involved in the regulation of c-myc expression is altered in tumor-derived cell lines.
38
Erisman, M. D., P. G. Rothberg, R. E. Diehl, C. C. Morse, J. M. Spandorfer, and S. M. Astrin. "Deregulation of c-myc gene expression in human colon carcinoma is not accompanied by amplification or rearrangement of the gene." Molecular and Cellular Biology 5, no. 8 (August 1985): 1969–76. http://dx.doi.org/10.1128/mcb.5.8.1969-1976.1985.
Full textAbstract:
The structure and expression of the c-myc oncogene were examined in 29 primary human colon adenocarcinomas. Dot blot hybridization of total RNA showed that 21 tumors (72%) had considerably elevated expression of c-myc (5- to 40-fold) relative to normal colonic mucosa. These data were corroborated by Northern blots of polyadenylated RNA, which showed a 2.3-kilobase transcript. Southern analysis of the c-myc locus in these tumors indicated the absence of amplification or DNA rearrangement in a 35-kilobase region encompassing the gene. In a parallel study, elevated expression of c-myc without amplification or DNA rearrangement was also observed in three of six colon carcinoma cell lines examined; in addition, unlike a normal colon cell line control, these three cell lines exhibited constitutive, high-level expression of the gene during their growth in cultures. These results indicate that elevated expression of the c-myc oncogene occurs frequently in primary human colon carcinomas and that the mechanism involved in the regulation of c-myc expression is altered in tumor-derived cell lines.
39
Ingvarsson, S., C. Asker, H. Axelson, G. Klein, and J. Sümegi. "Structure and expression of B-myc, a new member of the myc gene family." Molecular and Cellular Biology 8, no. 8 (August 1988): 3168–74. http://dx.doi.org/10.1128/mcb.8.8.3168.
Full textAbstract:
The myc family of genes contains five functional members. We describe the cloning of a new member of the myc family from rat genomic and cDNA libraries, designated B-myc. A fragment of cloned B-myc was used to map the corresponding rat locus by Southern blotting of DNA prepared from rat X mouse somatic cell hybrids. B-myc mapped to rat chromosome 3. We have previously mapped the c-myc to rat chromosome 7 (J. Sümegi, J. Spira, H. Bazin, J. Szpirer, G. Levan, and G. Klein, Nature [London] 306:497-498, 1983) and N-myc and L-myc to rat chromosomes 6 and 5, respectively (S. Ingvarsson, C. Asker, Z. Wirschubsky, J. Szpirer, G. Levan, G. Klein, and J. Sümegi, Somat. Cell Mol. Genet. 13:335-339, 1987). A partial sequence of B-myc had extensive sequence homology to the c-myc protein-coding region, and the detection of intron homology further indicated that these two genes are closely related. The DNA regions conserved among the myc family members, designated myc boxes, were highly conserved between c-myc and B-myc. A lower degree of homology was detected in other parts of the coding region in c-myc and B-myc not present in N-myc and L-myc. A 1.3-kilobase B-myc-specific mRNA was detected in most rat tissues, with the highest expression in the brain. This resembled the expression pattern of c-myc, although at different relative levels, and was in contrast to the more tissue-specific expression of N-myc and L-myc. B-myc was expressed at uniformly high levels in all fetal tissues and during subsequent postnatal development, in contrast to the stage-specific expression of c-myc.
40
Ingvarsson, S., C. Asker, H. Axelson, G. Klein, and J. Sümegi. "Structure and expression of B-myc, a new member of the myc gene family." Molecular and Cellular Biology 8, no. 8 (August 1988): 3168–74. http://dx.doi.org/10.1128/mcb.8.8.3168-3174.1988.
Full textAbstract:
The myc family of genes contains five functional members. We describe the cloning of a new member of the myc family from rat genomic and cDNA libraries, designated B-myc. A fragment of cloned B-myc was used to map the corresponding rat locus by Southern blotting of DNA prepared from rat X mouse somatic cell hybrids. B-myc mapped to rat chromosome 3. We have previously mapped the c-myc to rat chromosome 7 (J. Sümegi, J. Spira, H. Bazin, J. Szpirer, G. Levan, and G. Klein, Nature [London] 306:497-498, 1983) and N-myc and L-myc to rat chromosomes 6 and 5, respectively (S. Ingvarsson, C. Asker, Z. Wirschubsky, J. Szpirer, G. Levan, G. Klein, and J. Sümegi, Somat. Cell Mol. Genet. 13:335-339, 1987). A partial sequence of B-myc had extensive sequence homology to the c-myc protein-coding region, and the detection of intron homology further indicated that these two genes are closely related. The DNA regions conserved among the myc family members, designated myc boxes, were highly conserved between c-myc and B-myc. A lower degree of homology was detected in other parts of the coding region in c-myc and B-myc not present in N-myc and L-myc. A 1.3-kilobase B-myc-specific mRNA was detected in most rat tissues, with the highest expression in the brain. This resembled the expression pattern of c-myc, although at different relative levels, and was in contrast to the more tissue-specific expression of N-myc and L-myc. B-myc was expressed at uniformly high levels in all fetal tissues and during subsequent postnatal development, in contrast to the stage-specific expression of c-myc.
41
Ben-Porath, Ittai, Ofra Yanuka, and Nissim Benvenisty. "The Tmp Gene, Encoding a Membrane Protein, Is a c-Myc Target with a Tumorigenic Activity." Molecular and Cellular Biology 19, no. 5 (May 1, 1999): 3529–39. http://dx.doi.org/10.1128/mcb.19.5.3529.
Full textAbstract:
ABSTRACT The c-Myc oncoprotein induces cell proliferation and transformation through its activity as a transcription factor. Uncovering the genes regulated by c-Myc is an essential step for understanding these processes. We recently isolated the tumor-associated membrane protein gene, Tmp, from a c-myc-induced mouse brain tumor. Here we show that Tmp is specifically highly expressed in mammary tumors and T-cell lymphomas which develop in c-myc transgenic mice, suggesting that Tmpexpression is a general characteristic of c-Myc-induced tumors. In addition, Tmp expression is induced upon serum stimulation of fibroblasts as shown in a time course closely correlated with c-myc expression. We have isolated the Tmppromoter region and identified a putative c-Myc binding element, CACGTG, located in the first intron of the gene. We show here that constructs containing the Tmp regulatory region fused to a reporter gene are activated by c-Myc through this CACGTG element and that the c-Myc–Max protein complex can bind to this element. Moreover, an inducible form of c-Myc, the MycER fusion protein, can activate the endogenous Tmp gene. We also show that Tmp-overexpressing fibroblasts induce rapidly growing tumors when injected into nude mice, suggesting thatTmp may possess a tumorigenic activity. Thus, TMP, a member of a novel family of membrane glycoproteins with a suggested role in cellular contact, is a c-Myc target and is possibly involved in c-Myc-induced transformation.
42
Chen, Yili, Thomas W. Blackwell, Jing Gao, Anura Hewagama, Heather M. Grifka, Angel W. Lee, and David J. States. "Computational Prediction of c-MYC Binding and Action by Integration of Multiple Data Sources." Blood 108, no. 11 (November 16, 2006): 4345. http://dx.doi.org/10.1182/blood.v108.11.4345.4345.
Full textAbstract:
Abstract c-MYC is an important proto-oncogene. Its actions are mediated by sequence specific binding of the c-MYC protein to genomic DNA. While many c-MYC recognition sites can be identified in c-MYC responsive genes, many others are associated with genes showing no c-MYC response. It is not yet known how the cell determines which of the many c-MYC recognition sites are biologically active and directly bind c-MYC protein to regulate gene expression. We have developed a computational model that predict c-MYC binding and functional activation as distinct processes. Our model integrates four types of evidence to predict functional c-MYC targets: genomic sequence, MYC binding, gene expression and gene function annotations. First, a Bayesian network classifier is used to predict c-MYC recognition sites likely to exhibit high occupancy binding in chromatin immunoprecipitation studies using several types of sequence information, including predicted DNA methylation using a computational model to estimate the likelihood of genomic DNA methylation. In the second step, the DNA binding probability of MYC is combined with the gene expression information from 9 independent microarray datasets in multiple tissues and the gene function annotations in Gene Ontology to predict the c-MYC targets. The prediction results were compared with the c-MYC targets in public MYC target database [www.myccancergene.org], which collected the c-MYC targets identified in biomedical literatures. In total, we predicted 599 likely c-MYC genes on human genome, of which 73 have been reported to be both bound and regulated by MYC, 83 are bound by MYC in vivo and another 93 are MYC regulated. The approach thus successfully identified many known c-MYC targets as well as suggesting many novel sites including many sites that are remote from the transcription start site. Our findings suggest that to identify c-MYC genomic targets, any study based on single high throughput dataset is likely to be insufficient. Using multiple gene expression datasets helps to improve the sensitivity and integration of different data sources helps to improve the specificity. Summary of c-MYC Targets Prediction Microarray Dataset Data Source (Citation) Tissue Predicted Targets Binding&Regulation Reported Only Binding Reported Only Regulation Reported 1 PMID: 15778709 B Cell 421 61 60 56 2 PMID: 12086878 Prostate Cancer 428 56 65 76 3 PMID: 14722351 Prostate Cancer 50 4 7 13 4 PMID: 15254046 Prostate Cancer 66 19 8 14 5 PMID: 12747878 Breast Cancer 17 1 3 5 6 PMID: 11707567 Lung Cancer 295 51 42 59 7 PMID: 15820940 CML 8 1 1 2 8 PMID: 12704389 ALL 222 45 32 46 9 PMID: 11731795 ALL / MLL / AML 22 6 1 6 Total 599 73 83 93
43
Hansen, L. J., B. C. Tennant, C. Seeger, and D. Ganem. "Differential activation of myc gene family members in hepatic carcinogenesis by closely related hepatitis B viruses." Molecular and Cellular Biology 13, no. 1 (January 1993): 659–67. http://dx.doi.org/10.1128/mcb.13.1.659.
Full textAbstract:
Woodchucks infected with woodchuck hepatitis virus (WHV) and ground squirrels infected with ground squirrel hepatitis virus (GSHV) both develop hepatocellular carcinoma (HCC), but WHV-associated tumors arise more frequently and much earlier in life. These differences are preserved when the oncogenic potentials of the two viruses are examined in the same host (woodchucks). We examined RNA and genomic DNA from tumors arising from WHV- and GSHV-infected woodchucks to determine whether these viruses use the same oncogenic pathway. N-myc RNA was not expressed in normal liver but was expressed in 10 of 13 WHV-associated HCCs examined. Southern blot analysis showed that 7 of 17 WHV-induced tumors (41%) contained rearrangements at N-myc loci due to viral genomic integration. Six of these seven inserts affected N-myc2, and most of these were at the 5' end of the gene. In contrast, only two of seven GSHV-induced woodchuck HCCs expressed N-myc RNA, and only 1 of the 16 tumors (6%) contained a rearranged N-myc allele. The GSHV-associated HCCs all contained numerous viral insertions, so the low frequency of integration into N-myc loci by GSHV was not due to a general block to integration. Four of sixteen GSHV-induced tumors harbored amplified c-myc alleles, and five of seven GSHV tumors tested contained elevated c-myc RNA levels. By contrast, enhanced c-myc RNA levels were observed in only 2 of 13 WHV-induced HCC. We conclude that N-myc overexpression is a regular feature of WHV- but not GSHV-associated hepatocarcinogenesis in a common host. In contrast, c-myc transcriptional deregulation is rarely encountered in WHV-induced HCC but is frequent in GSHV-induced HCC.
44
Hansen, L. J., B. C. Tennant, C. Seeger, and D. Ganem. "Differential activation of myc gene family members in hepatic carcinogenesis by closely related hepatitis B viruses." Molecular and Cellular Biology 13, no. 1 (January 1993): 659–67. http://dx.doi.org/10.1128/mcb.13.1.659-667.1993.
Full textAbstract:
Woodchucks infected with woodchuck hepatitis virus (WHV) and ground squirrels infected with ground squirrel hepatitis virus (GSHV) both develop hepatocellular carcinoma (HCC), but WHV-associated tumors arise more frequently and much earlier in life. These differences are preserved when the oncogenic potentials of the two viruses are examined in the same host (woodchucks). We examined RNA and genomic DNA from tumors arising from WHV- and GSHV-infected woodchucks to determine whether these viruses use the same oncogenic pathway. N-myc RNA was not expressed in normal liver but was expressed in 10 of 13 WHV-associated HCCs examined. Southern blot analysis showed that 7 of 17 WHV-induced tumors (41%) contained rearrangements at N-myc loci due to viral genomic integration. Six of these seven inserts affected N-myc2, and most of these were at the 5' end of the gene. In contrast, only two of seven GSHV-induced woodchuck HCCs expressed N-myc RNA, and only 1 of the 16 tumors (6%) contained a rearranged N-myc allele. The GSHV-associated HCCs all contained numerous viral insertions, so the low frequency of integration into N-myc loci by GSHV was not due to a general block to integration. Four of sixteen GSHV-induced tumors harbored amplified c-myc alleles, and five of seven GSHV tumors tested contained elevated c-myc RNA levels. By contrast, enhanced c-myc RNA levels were observed in only 2 of 13 WHV-induced HCC. We conclude that N-myc overexpression is a regular feature of WHV- but not GSHV-associated hepatocarcinogenesis in a common host. In contrast, c-myc transcriptional deregulation is rarely encountered in WHV-induced HCC but is frequent in GSHV-induced HCC.
45
Liu, Lan, Li Li, Jaladanki N. Rao, Tongtong Zou, Huifang M. Zhang, Dessy Boneva, Marasa S. Bernard, and Jian-Ying Wang. "Polyamine-modulated expression of c-myc plays a critical role in stimulation of normal intestinal epithelial cell proliferation." American Journal of Physiology-Cell Physiology 288, no. 1 (January 2005): C89—C99. http://dx.doi.org/10.1152/ajpcell.00326.2004.
Full textAbstract:
The nuclear protein c-Myc is a transcription factor involved in the control of cell cycle. Our previous studies indicated that cellular polyamines are absolutely required for cell proliferation in crypts of small intestinal mucosa and that polyamines have the ability to stimulate expression of the c- myc gene. The current study went further to determine whether induced nuclear c-Myc plays a role in stimulation of cell proliferation by polyamines in intestinal crypt cells (IEC-6 line). Exposure of normal quiescent cells after 24-h serum deprivation to 5% dialyzed fetal bovine serum (dFBS) increased both cellular polyamines and expression of the c- myc gene. Increased c-Myc protein formed heterodimers with its binding partner, Max, and specifically bound to the Myc/Max binding site, which was associated with an increase in DNA synthesis. Depletion of cellular polyamines by pretreatment with α-difluoromethylornithine (DFMO) prevented increases in c- myc expression and DNA synthesis induced by 5% dFBS. c- Myc gene transcription and cell proliferation decreased in polyamine-deficient cells, whereas the natural polyamine spermidine given together with DFMO maintained c- myc gene expression and cell growth at normal levels. Disruption of c- myc expression using specific c- myc antisense oligomers not only inhibited normal cell growth (without DFMO) but also prevented the restoration of cell proliferation by spermidine in polyamine-deficient cells. Ectopic expression of wild-type c- myc by recombinant adenoviral vector containing c- myc cDNA increased cell growth. These results indicate that polyamine-induced nuclear c-Myc interacts with Max, binds to the specific DNA sequence, and plays an important role in stimulation of normal intestinal epithelial cell proliferation.
46
Su, Tsung-Sheng, Ling-Huang Lin, Wing-Yiu Lui, Chungming Chang, Chen-Kung Chou, Ling-Pei Ting, Cheng-Po Hu, Shou-Hwa Han, and Fang-Ku P'eng. "Expression of c-myc gene in human hepatoma." Biochemical and Biophysical Research Communications 132, no. 1 (October 1985): 264–68. http://dx.doi.org/10.1016/0006-291x(85)91017-4.
Full text
47
Piechaczyk, Marc, Jean-Marie Blanchard, and Philippe Jeanteur. "c-myc gene regulation still holds its secret." Trends in Genetics 3 (January 1987): 47–51. http://dx.doi.org/10.1016/0168-9525(87)90166-1.
Full text
48
Zhang, Yangyang, and Fan Dong. "Gfi1 Upregulates c-Myc Expression and Promotes c-Myc-Driven Cell Proliferation." Blood 134, Supplement_1 (November 13, 2019): 3769. http://dx.doi.org/10.1182/blood-2019-124833.
Full textAbstract:
Gfi1 is a zinc-finger transcriptional repressor that plays an important role in hematopoiesis. When aberrantly activated, Gfi1 may function as a weak oncoprotein in the lymphoid system, but collaborate strongly with c-Myc in lymphomagenesis. c-Myc is a transcription factor that is frequently activated in human cancers including leukemia and lymphoma mainly due to its overexpression as a result of gene amplifications and chromosomal translocations. c-Myc overexpression may also result from stabilization of c-Myc protein, which is highly unstable and rapidly degraded through the ubiquitin-proteasome pathway. The mechanism by which Gfi1 collaborates with c-Myc in lymphomagenesis is incompletely understood. c-Myc activates gene expression by forming a heterodimeric complex with the partner protein Max, but may also repress target genes through interaction with transcription factor Miz-1. We previously showed that Gfi1 indirectly interacts with c-Myc through Miz-1 and collaborates with c-Myc to repress CDK inhibitors p21Cip1 and p15Ink4B. In this study, we show that Gfi1 augmented the level of c-Myc protein transiently expressed in Hela cells and the levels of MycER fusion protein stably expressed in the mouse pro-B Ba/F3 and myeloid 32D cells. The C-terminal ZF domains of Gfi1, but not its transcriptional repression and DNA binding activities, were required for c-Myc upregulation. Notably, although Miz-1 has been shown to stabilize c-Myc protein, the expression of c-Myc V394D mutant, which is defective in Miz-1 interaction, was still upregulated by Gfi1, suggesting that Gfi1-mediated c-Myc upregulation was independent of Miz-1 interaction. We further show that Gfi1 overexpression led to reduced polyubiquitination and increased stability of c-Myc protein. Interestingly, the levels of endogenous c-Myc mRNA and protein were augmented upon induction of Gfi1 expression in Ba/F3 and Burkitt lymphoma Ramos cells transduced with the doxycycline-inducible Gfi1 lentiviral construct, but reduced in Gfi1-knocked down human leukemic HL60 and U937 cells. Additionally, targeted deletion of Gfi1 resulted in reduced c-Myc expression in mouse lineage negative bone marrow cells, which was associated with a decline in the expression of c-Myc-activated target genes. The oncogenic potential of Myc derives from its ability to stimulate cell proliferation. Our results demonstrate that inducible expression of Gfi1 in Ba/F3 cells expressing MycER promoted Myc-driven cell cycle progression and proliferation. Thus, in addition to its role in c-Myc-mediated transcriptional repression, Gfi1 upregulates c-Myc expression at both mRNA and protein levels, leading to enhanced expression of c-Myc-activated genes and augmented cell proliferation driven by c-Myc. Together, these data may reveal a novel mechanism by which Gfi1 collaborates with c-Myc in lymphomagenesis. Disclosures No relevant conflicts of interest to declare.
49
Liu, Lan, Jaladanki N. Rao, Tongtong Zou, Lan Xiao, Alexis Smith, Ran Zhuang, Douglas J. Turner, and Jian-Ying Wang. "Activation of Wnt3a signaling stimulates intestinal epithelial repair by promoting c-Myc-regulated gene expression." American Journal of Physiology-Cell Physiology 302, no. 1 (January 2012): C277—C285. http://dx.doi.org/10.1152/ajpcell.00341.2011.
Full textAbstract:
In response to mucosal injury, epithelial cells modify the patterns of expressed genes to repair damaged tissue rapidly. Our previous studies have demonstrated that the transcription factor c-Myc is necessary for stimulation of epithelial cell renewal during mucosal healing, but the up-stream signaling initiating c-Myc gene expression after injury remains unknown. Wnts are cysteine-rich glycoproteins that act as short-range ligands to locally activate receptor-mediated signaling pathways and correlate with the increased expression of the c-Myc gene. The current study tested the hypothesis that Wnt3a signaling is implicated in intestinal epithelial repair after wounding by stimulating c-Myc expression. Elevated Wnt3a signaling in intestinal epithelial cells (IEC-6 line) by coculturing with stable Wnt3a-transfected fibroblasts or ectopic overexpression of the Wnt3a gene enhanced intestinal epithelial repair after wounding. This stimulatory effect on epithelial repair was prevented by silencing the Wnt coreceptor LRP6 or by c-Myc silencing. Activation of the Wnt3a signaling pathway increased β-catenin nuclear translocation by decreasing its phosphorylation and stimulated c-Myc expression during epithelial repair after wounding. In stable Wnt3a-transfected IEC-6 cells, increased levels of c-Myc were associated with an increase in expression of c-Myc-regulated genes cyclcin D1 and cyclin E, whereas c-Myc silencing inhibited expression of cyclin D1 and cyclin E and delayed epithelial repair. These results indicate that elevated Wnt3a signaling in intestinal epithelial cells after wounding stimulates epithelial repair by promoting c-Myc-regulated gene expression.
50
Suen, T. C., and M. C. Hung. "c-myc reverses neu-induced transformed morphology by transcriptional repression." Molecular and Cellular Biology 11, no. 1 (January 1991): 354–62. http://dx.doi.org/10.1128/mcb.11.1.354.
Full textAbstract:
Amplification or overexpression or both of either the c-myc or the human neu (C-erbB-2) gene are common events in many primary human tumors. Coamplification or overexpression or both of both genes have been reported in some breast cancers. The possibility of cooperation between the c-myc and the normal rat neu (c-neu) genes in transforming cells was examined. Surprisingly, the expression of c-myc in B104-1-1 cells, and activated rat neu oncogene (neu*)-transformed NIH 3T3 line, resulted in morphologic reversion. This reversion was found to be a consequence of a transcription-repressive action of c-myc on the neu gene via a 140-bp fragment on the neu gene promoter. The effective concentration of a positive factor(s) interacting with this fragment seemed to be lowered by the expression of c-myc. Our findings lend support to arguments concerning the long-suspected function of c-myc as a transcriptional modulator. They also imply that an oncogene such as c-myc, or possibly the rapidly explored class that encodes transcription factors, under certain conditions may act to reverse a transformed phenotype that is induced by another oncogene instead of contributing positively towards the transformation process. Therefore, the activity of an oncogene may depend on the environment in which it is expressed. In addition, we may have identified the neu gene as a cellular target gene of negative regulation by c-myc.