Cyclin D2 and Ha-Ras transformed rat embryo fibroblasts exhibit a novel deregulation of cell size control and early S phase arrest in low serum.

摘要: The D-type cyclins are growth factor-regulated delayed early functions which peak at the G1/S transition, thought to regulate entry into S phase and have been implicated in tumorigenesis. Here, we show that cyclin D2 can co-operate with Ha-Ras impose a novel transformed state on rat embryo fibroblasts (REF). While clonal D2/Ha-Ras REF transformants exhibit characteristic phenotype high serum, low serum they arrest cell proliferation display profound morphological cytological changes indicating loss of control mass deregulation transition. Notably, despite re-establishment actin cables proliferation, continues increase, creating giant cells up 10 x normal size. Also, during low-serum culture make very gradual but progressive phase, reaching 2.4N DNA content after 6 days. PCNA is expressed 2N 4N largely absent, thus undergo arrest. transfer induced retinoblastoma protein enter its dephosphorylated state, A, B cdc2 levels decrease, all as normal, E, cdk4, cdk2 exogenous persisted levels. These results indicate transform when mitogenic signals from factors provided. However, co-operation provides only subset progression these sufficient for G1-related increase entry, insufficient full cycling.