Ras and Myc can drive oncogenic cell proliferation through individual D-cyclins.
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.
Yu
Qunyan
Q
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Ciemerych
Maria A
MA
Sicinski
Piotr
P
D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D019938:Cyclin D1 / Q000235:genetics / Q000502:physiology*; D056742:Cyclin D2; D056743:Cyclin D3; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D011905:Genes, ras / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*
C486196:Ccnd2 protein, mouse; C534697:Ccnd3 protein, mouse; D056742:Cyclin D2; D056743:Cyclin D3; D016213:Cyclins; D016271:Proto-Oncogene Proteins c-myc; D019938:Cyclin D1