The role of c-myc in cellular growth control

Schmidt, Emmett V.

doi:10.1038/sj.onc.1202751

Cited by 347 publications

(258 citation statements)

References 103 publications

(79 reference statements)

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“…In the epithelial cells from tgfa/c-myc dual transgenic mice (lower panel), TGFa (a) induces overexpression of cyclin D1 and cooperates with c-Myc to induce overexpression of cyclin E and sporadic loss of pRB. These e ects, together with the c-Myc-induced elevation of E2F1 and cyclin A2, elicit early onset of very aggressive tumor phenotypes in the bi-transgenic model ras) greatly enhances its transforming e cacy (Valverius et al, 1990;Schmidt, 1999;Facchini et al, 1998;Amati et al, 1998;Dang, 1999;Nass et al, 1997). The reciprocal expression of c-Myc and cyclins D1 and E in c-myc tumors and the co-expression of these genes in tgfa/cmyc tumors raise the possibility that one role of these additional factors may be to rescue the expression of cyclin D1 and/or cyclin E. Overexpression of these cyclins may be bene®cial for the transformation, but it may be hampered because of constantly high levels of c-Myc.…”

Section: Discussionmentioning

confidence: 99%

“…The c-Myc protein plays a crucial role in cell proliferation, di erentiation, apoptosis, and transformation (Schmidt, 1999;Facchini et al, 1998;Amati et al, 1998;Dang, 1999). Overexpression, ampli®cation, or rearrangement of the c-myc gene has been reported in over 50% of human breast cancer cases (Nass et al, 1997;Amundadottir et al, 1996a).…”

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: Introductionmentioning

confidence: 99%

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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“…It has been estimated that proliferating cells expend more than 80% of their cellular energy on the synthesis, transport, processing and assembly of ribosomal subunits. 7 Coordination of synthesis occurs in the nucleolus, a nuclear suborganelle where rRNA is transcribed, processed, and assembled with ribosomal proteins to produce ribosomal subunits. The process of translation and ribosomal biogenesis is tightly regulated at a variety of levels and can therefore respond dynamically to cellular stimuli delivered through growth factor receptors and nutrient sensors.…”

Section: Control Of Ribosome Biogenesismentioning

confidence: 99%

Translational research? Ribosome integrity and a new p53 tumor suppressor checkpoint

Opferman

Zambetti²

2006

Cell Death Differ

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The p53 tumor suppressor senses a variety of cellular stresses, such as DNA damage and inappropriate proliferation, and responds accordingly by inducing cell cycle arrest or apoptosis. The ability of p53 to regulate cell division and survival is considered essential for blocking tumor development. A recent article by Sulic et al. 18 provides convincing genetic evidence that p53 also surveils the state of protein synthesis. Here, we focus on how p53 may detect alterations in translation and the consequence of this monitoring process on maintaining normal cell homeostasis.

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“…c-Myc encodes a nuclear phospho-protein that plays an active role in cellular functions, such as proliferation, differentiation, and apoptosis (Schmidt, 1999). Overexpression of c-Myc leads to shortening of the G1 phase of the cell cycle and inhibition of differentiation (Karn et al, 1989).…”

Section: Molecular Biology Of the Cell 1036mentioning

confidence: 99%

Loss of Caveolin-1 Gene Expression Accelerates the Development of Dysplastic Mammary Lesions in Tumor-Prone Transgenic Mice

Williams

Cheung

Park

et al. 2003

MBoC

136

101

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Caveolin-1 is the principal structural component of caveolae microdomains, which represent a subcompartment of the plasma membrane. Several independent lines of evidence support the notion that caveolin-1 functions as a suppressor of cell transformation. For example, the human CAV-1 gene maps to a suspected tumor suppressor locus (D7S522/7q31.1) that is frequently deleted in a number of carcinomas, including breast cancers. In addition, up to 16% of human breast cancers harbor a dominant-negative mutation, P132L, in the CAV-1 gene. Despite these genetic associations, the tumor suppressor role of caveolin-1 still remains controversial. To directly assess the in vivo transformation suppressor activity of the caveolin-1 gene, we interbred Cav-1 (Ϫ/Ϫ) null mice with tumor-prone transgenic mice (MMTV-PyMT) that normally develop multifocal dysplastic lesions throughout the entire mammary tree. Herein, we show that loss of caveolin-1 gene expression dramatically accelerates the development of these multifocal dysplastic mammary lesions. At 3 wk of age, loss of caveolin-1 resulted in an approximately twofold increase in the number of lesions (foci per gland; 3.3 Ϯ 1.0 vs. 7.0 Ϯ 1.2) and an approximately fiveto sixfold increase in the total area occupied by these lesions. Similar results were obtained at 4 wk of age. However, complete loss of caveolin-1 was required to accelerate the appearance of these dysplastic mammary lesions, because Cav-1 (ϩ/Ϫ) heterozygous mice did not show any increases in foci development. We also show that loss of caveolin-1 increases the extent and the histological grade of these mammary lesions and facilitates the development of papillary projections in the mammary ducts. Finally, we demonstrate that cyclin D1 expression levels are dramatically elevated in Cav-1 (Ϫ/Ϫ) null mammary lesions, consistent with the accelerated appearance and growth of these dysplastic foci. This is the first in vivo demonstration that caveolin-1 can function as a transformation suppressor gene. INTRODUCTIONCaveolae are 50 -100-nm plasma membrane microdomains that function in vesicular trafficking and signal transduction (Galbiati et al., 2001). Approximately 10 years ago, the principal structural component of caveolae was identified as a 21-to 24-kDa integral membrane protein and termed caveolin (Glenney and Zokas, 1989;Rothberg et al., 1992) (now referred to as caveolin-1) (Scherer et al., 1996).Caveolin-1 is expressed in numerous cell types, including fibroblasts, adipocytes, smooth muscle cells, endothelial cells, and epithelial cells . Interestingly, caveolin-1 was first described as a major substrate of the DOI: 10.1091/mbc.E02-08 -0503.¶ Corresponding author. E-mail address: lisanti@aecom.yu.edu. © 2003 by The American Society for Cell Biology 1027v-Src tyrosine kinase in Rous sarcoma virus-transformed fibroblasts, suggesting that caveolin-1 may be a target for modification or inactivation by activated oncogenes . Subsequent cell culture experiments demonstrated that caveolin-1 mRNA and protein expression lev...

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The role of c-myc in cellular growth control

Cited by 347 publications

References 103 publications

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

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

Translational research? Ribosome integrity and a new p53 tumor suppressor checkpoint

Loss of Caveolin-1 Gene Expression Accelerates the Development of Dysplastic Mammary Lesions in Tumor-Prone Transgenic Mice

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