AbstractsBiology & Animal Science

Prostate cancer is one of the most frequently diagnosed cancers and second highest cause of death in patients who suffer from cancer in western countries. Much effort has been carried out to understand the molecular mechanisms of prostate cancer; however these are still unclear. The kallikrein (KLK) family has been implicated in prostate cancer. The KLK family is a subgroup of serine proteases shown to have diverse physiological functions with 15 KLK genes have been identified until now. Growing evidence suggests that many KLKs are implicated in carcinogenesis; for example, KLK3 (also called prostate specific antigen (PSA)) is commonly used as a prostate cancer biomarker. KLK4 is another member of the family whose expression is hormonally regulated by androgens. KLK4 is primarily localized in the nucleus, which differs from the other members of this family that are, or thought to be, secreted proteins. Previous studies from our laboratory have shown that KLK4 promotes prostate cancer cell proliferation. In this study, KLK4 was ectopically expressed, as well as knocked down by shRNA, in different prostate cancer cell lines. The expression of different cell cycle related and androgen regulated genes were determined by qPCR to further elucidate the role of KLK4 in prostate carcinogenesis. KLK4 knockdown reduced the growth rate of LNCaP cells and altered the expression of PCNA, Vimentin and E2F1, genes involved in cell cycle/proliferation, further supporting the hypothesis that KLK4 plays an important role in prostate cancer cell proliferation. Unexpectedly, KLK4 knockdown in LNCaP cells deregulated AR target gene expression in a differential manner. These data support earlier findings and suggest that KLK4 has an integral role in prostate cancer cell growth.