Livin-alpha Promotes Cell Proliferation by Regulating G(1)-S Cell Cycle Transition in Prostate Cancer

BACKGROUND. Prostate cancer is the third most common cancer and the second leading cause of cancer death for males in US. Livin has recently been described as a cancer-associated member of inhibitor of apoptosis proteins family, highly expressed in prostate cancer. Livin gene encodes two splicing variants, termed Livin-alpha and Livin-beta. We hypothesized that deregulation of proliferation could be due in part to Livin expression. METHODS. Pathological analysis of Livin was performed in 20 prostate cancer tissues and 5 benign prostatic hyperplasia tissues. The expression of Livin isoforms was also investigated by Western blot in prostate cancer cell lines LNCaP and PC3. The role of Livin-alpha in vitro was further studied. Using Livin-alpha knockdown and overexpression models, cell cycle analysis, Ki-67 immunocytostaining, and MTT assay were performed respectively. RESULTS. Livin expression positive ratio was shown to be 5.4%, 23.6%, 52.4%, 73.4% in benign prostatic hyperplasia, low, medium, and high grade of prostate cancer respectively, and Livin was positively correlated with clinical pathological grades of prostate cancer. Livin-alpha was expressed in both LNCaP and PC3; meanwhile; Livin-beta was only detected in the PC3. Livin-alpha siRNA not only resulted inG(1)-S cell cycle arrest, but also strongly correlated with the descended proliferation index and survival rate in LNCaP. In comparison, overexpression of Livin-alpha resulted in an accelerated S phase entry combined with elevated proliferation index and survival in LNCaP. CONCLUSIONS. Livin-alpha may promote cell proliferation by regulating G(1)-S cell cycle transition and possibly play an important part in initiation of prostate cancer. Prostate 71: 4251, 2011. (C) 2010 Wiley-Liss, Inc.