UPREGULATION OF CKI P21 BY ANDROGEN IN PROSTATE CANCER

描述

DESCRIPTION The prostate cancer is the second leading cause of cancer death in men. At early stage, the growth of prostate cancer is androgen-dependent and castration has been a very effective method in treating prostate cancer. Development of androgen-independent growth of prostate cancer after approximately 18 months of hormone ablation therapy is a major clinical dilemma. Goal of this study is to investigate the molecular mechanisms of CKI p21/Cip1/Waf1 in androgen-dependent and -independent growth of prostate carcinoma cells. This study is based on our observations that p21/Cip1/Waf1 gene was up-regulated by androgen and an increased basal expression of the gene was found in an androgen-independent prostate cancer cell line. This proposal will investigate the anti-apoptosis function of p21/Cip1/Waf1 gene in prostate carcinoma cells, which may confer the homeostasis of the cells in androgen-dependent manner and development of androgen-independent growth of pro-static cancer cell by increased basal expression of the gene. The molecular mechanism of androgen action on p21/Cip1/Waf1 gene expression will be elucidated. In addition, an in vivo androgen-independent prostate cancer model will be established for future therapeutic studies. Finally, the expression of the p21/Cip1/Waf1 gene in androgen-dependent and -independent prostate cancer specimens will be evaluated. If indeed an increased basal level of p21/Cip1/Waf1 gene in androgen-independent prostate cancer specimens was observed, it can be served as a clinical marker for developing androgen-dependent growth of prostate cancer.