Androgen Mediated Regulation of the G1-S Transition in Prostate Cancer

Prostatic adenocarcinoma is the most frequently diagnosed malignancy in the United States and is the second leading cause of cancer deaths among men (Landis et al., 1998). Most prostate cancers are treated by androgen ablation, since androgen is a required mitogen for the survival and proliferation of prostate cells (Cunha et al., 1987; Jenster, 1999; Klotz, 2000; Labrie, 2000). This treatment is initially effective, as upon androgen withdrawal most prostate cancer cells undergo cell cycle arrest or cell death (Denmeade et al., 1996; Murphy et al., 1991; Westin et al., 1995). Unfortunately, androgen independent tumors arise and lead to patient morbidity. Determination of how androgen exerts its effect as a mitogen in early prostate cancer, and how the androgen requirement is subverted in advanced disease is the focus of intensive research.