Mysterious liaisons: the relationship between c-Myc and the cell cycle

Obaya, Álvaro J.; Mateyak, Maria K.; Sedivy, John M.

doi:10.1038/sj.onc.1202749

Cited by 203 publications

(178 citation statements)

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“…This is surprising, as suppression of cyclin E by c-Myc has not been reported, and relevant literature suggests that c-Myc can activate expression of cyclin E in vitro (Amati et al, 1998;Obaya et al, 1999). Several studies have suggested that cyclin D1/cdk4 should be activated prior to the onset of cyclin E/cdk2 activity in order to ensure an orderly transition to S phase (Obaya et al, 1999;Prall et al, 1998). Thus, it is possible that the lack of a su cient amount of cyclin D1 may hamper the expression of cyclin E. It is even possible that prevention of expression of cyclin E may facilitate the cell growth during the early stages of the carcinogenic process in c-myc animals, as it has been shown that stable overexpression of cyclin E, rendered by cDNA transfection, inhibits growth of mammary epithelial cells (Sgambato et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Thus, cdc25A and cyclins E and A2 have been suggested as direct, c-Myc-activated target genes (Cole et al, 1999;Obaya et al, 1999). In contrast, the relationship between c-Myc and cyclin D1 is still under debate in the literature (Facchini et al, 1998;Dang, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Cell cycle basis for the onset and progression of c-Myc-induced, TGFα-enhanced mouse mammary gland carcinogenesis

et al. 2000

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Using single and double transgenic mouse models, we investigated how c-Myc modulates the mammary epithelial cell cycle to induce cancer and how TGFa enhanced the process. In c-myc transgenic mice, c-myc expression was high in the hyperplastic mammary epithelium and in the majority of tumor areas. However, the tumors displayed focal areas of low expression of cmyc but high rates of proliferation. In contrast to E2F1 and cyclin A2, which were induced and co-localized with c-myc expression, induction of cyclins D1 and E occurred only in these tumor foci. Overexpression of cyclin D1 also occurred in the hyperplastic epithelium of tgfa-single and tgfa/c-myc-double transgenic mice. In tgfa/c-myc tumors, cells positive for cyclins D1 and E were randomly spread, without showing a reciprocal relationship to c-myc expression. In contrast to c-myc tumors, most tgfa/c-myc tumors showed undetectable levels of retinoblastoma protein (pRB), and the loss of pRB occurred in some cases at the mRNA level. These results suggest that E2F1 and cyclin A2 may be induced by c-Myc to mediate the onset of mammary cancer, whereas overexpression of cyclins D1 and E may occur later to facilitate tumor progression. TGFa may play its synergistic role, at least in part, by inducing cyclin D1 and facilitating the loss of pRB.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Cell cycle basis for the onset and progression of c-Myc-induced, TGFα-enhanced mouse mammary gland carcinogenesis

et al. 2000

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“…Mad was a candidate repressor identi®ed in a gene screen for hTERT regulators (Oh et al, 2000) and a rise in endogenous Mad RNA and protein levels was inversely correlated with hTERT RNA levels (Gunes et al, 2000;Oh et al, 2000;Xu et al, 2001). Finally, while c-Myc protein was found associated with the hTERT gene in vivo in telomerase-positive promyelocytic leukemia HL60 cells as determined in chromatin immunoprecipitation assays (Xu et al, 2001) (Grandori et al, 2000;Obaya et al, 1999), but there is no evidence that this change is su cient to induce hTERT expression. (3) Overexpression of HPV16 E7, which is important for immortalization of keratinocytes, induces high level of c-Myc protein but is unable to activate telomerase expression (Gewin and Galloway, 2001;Veldman et al, 2001).…”

Section: Screening Candidate Moleculesmentioning

confidence: 99%

Regulation of the human telomerase reverse transcriptase gene

Ducrest¹,

Szutorisz²,

Lingner³

et al. 2002

Oncogene

178

144

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Most somatic human cells lack telomerase activity because they do not express the telomerase reverse transcriptase (hTERT) gene. Conversely, most cancer cells express hTERT and are telomerase positive. For most tumors it is not clear whether hTERT expression is due to their origin from telomerase positive stem cells or to reactivation of the gene during tumorigenesis. Telomerase negative cells lack detectable cytoplasmic and nuclear hTERT transcripts; in telomerase positive cells 0.2 to 6 mRNA molecules/cell can be detected. This suggests that expression is regulated by changes in the rate of hTERT gene transcription. In tumor cell lines hTERT expression behaves like a recessive trait, indicating that lack of expression in normal cells is due to one or several repressors. Studies with monochromosomal hybrids indicate that several chromosomes may code for such repressors. A number of transcription factors, tumor suppressors, cell cycle inhibitors, cell fate determining molecules, hormone receptors and viral proteins have been implicated in the control of hTERT expression; but these studies have not yet provided a clear explanation for the tumor speci®c expression of the hTERT gene, and the cis-acting elements which are the targets of repression in normal cells still have to be identi®ed.

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“…The c-myc proto-oncogene encodes a transcription factor which regulates the expression of many genes involved in the control of cell proliferation, differentiation and apoptosis (Ryan and Birnie, 1996;Obaya et al, 1999). c-myc gene expression is controlled at many levels (Marcu et al, 1992;Willis, 1999).…”

Section: Introductionmentioning

confidence: 99%