Livin-α Promotes Cell Proliferation by Regulating G1-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-α and Livin-β. 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-α in vitro was further studied. Using Livin-α 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-α was expressed in both LNCaP and PC3; meanwhile; Livin-β was only detected in the PC3. Livin-α siRNA not only resulted in G(1)-S cell cycle arrest, but also strongly correlated with the descended proliferation index and survival rate in LNCaP. In comparison, overexpression of Livin-α resulted in an accelerated S phase entry combined with elevated proliferation index and survival in LNCaP.

Conclusions: Livin-α may promote cell proliferation by regulating G(1)-S cell cycle transition and possibly play an important part in initiation of prostate cancer.