Oncogenic aberrations of p16INK4/CDKN2 and cyclin D1 cooperate to deregulate G1 control.

摘要: The p16INK4/CDKN2, D-type cyclins, their partner cyclin-dependent kinases, and retinoblastoma protein constitute a G1 regulatory pathway commonly targeted in oncogenesis. We show that, unexpectedly, abnormalities of p16INK4/CDKN2 occur concomitantly two-thirds cancer cell lines harboring aberrations cyclin D1. Gene transfer experiments demonstrated that concurrent alterations D1 p16 levels cooperate to (de)regulate control diploid fibroblasts, both events influence growth (RB)-positive, but not RB-deficient cells. These results biological consequences deregulating individual components along the are unequal, reflecting hierarchical roles checkpoint control. Whereas RB defects eliminate completely, upstream components, such as can multistep tumorigenesis.