Ras and Myc can drive oncogenic cell proliferation through individual D-cyclins

• Published in: Oncogene Vol. 24; no. 47; pp. 7114 - 7119
• Main Authors: QUNYAN YU, CIEMERYCH, Maria A, SICINSKI, Piotr
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 27.10.2005; Nature Publishing Group
• Subjects: Animals; Binding sites; Biological and medical sciences; Biology; Cancer; Cell Cycle; Cell growth; Cell physiology; Cell Proliferation; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Neoplastic; Cyclin D; Cyclin D1; Cyclin D1 - genetics; Cyclin D1 - physiology; Cyclin D2; Cyclin D3; Cyclins - genetics; Cyclins - physiology; Fibroblasts; Fibroblasts - cytology; Fibroblasts - metabolism; Fundamental and applied biological sciences. Psychology; Genes, ras - physiology; Kinases; Mice; Mice, Knockout; Molecular and cellular biology; Myc protein; Proto-Oncogene Proteins c-myc - physiology; Transcription; Transcription factors; Beijing China; United States > US; China; Massachusetts; Cell proliferation; Ras; Myc; oncogenic transformation; Cyclin D; Onc gene; Carcinogenesis; D-cyclins
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1208853

D-type cyclins serve as cell cycle recipients of several oncogenic pathways. The specific sequences of the promoters of the cyclin D genes are thought to render particular D-cyclins responsive to specific oncogenic pathways. For instance, the Ras oncogene was postulated to signal through cyclin D1, while Myc can impact the cell cycle machinery by transcriptionally upregulating cyclin D2. In the current study we engineered mouse fibroblasts to express only cyclin D1, only D2, or only D3. These 'single-cyclin' cells allowed us to rigorously test the ability of cyclin D1, D2, or D3, when expressed on their own, to serve as recipients of the Ras- and Myc-driven oncogenic pathways. We found that each of the D-cyclins was sufficient to drive oncogenic proliferation of mouse fibroblasts. This, together with our recent observations that cells lacking all three D-cyclins show greatly reduced susceptibility to the oncogenic action of Ras and Myc, reveals that the Ras and Myc oncogenes can impact the core cell cycle machinery through all three D-cyclins.