Downregulation of both p21/Cip1 and p27/Kip1 produces a more aggressive prostate cancer phenotype.

摘要: Roles of cyclin dependent kinase inhibitors, p21/Cip1 (p21) and p27/Kip1 (p27) in prostate cancer (PCa) progression is still not clear. Lower p27 protein expression PCa tissues often associated with poor prognosis, but prognostic significance p21 controversial. Herein, we investigated the role these molecules determining growth characteristics. We generated human DU145 cell variants knocked down levels (DU-p21) or (DU-p27), both (DU-p21+p27) via retroviral transduction respective shRNAs compared their various characteristics empty vector-transduced (DU-EV) cells vitro as well vivo. Knocking either did show any significant change doubling time, clonogenicity cycle cells, simultaneous knock-down significantly enhanced parameters. In athymic mice, DU-p21+p27 tumors showed higher rate than comparable DU-EV, DU-p21 DU-p27 tumors. Concurrently, had proliferation rate, showing 54% 48% increase proliferating nuclear antigen (PCNA) Ki-67-positive respectively, to DU-EV also microvessel density increased vascular endothelial factor (VEGF). Proliferation angiogenic status was Both vivo results implicate that have compensatory roles advanced ablation down-modulation essentially enhances aggressive carcinoma phenotype.