Prostate specific antigen gene regulation by androgen receptor

Prostate specific antigen (PSA) is a serine protease that is synthesized by both normal and malignant epithelial cells of the human prostate. PSA expressed by malignant cells, however, are released into the serum at an increased level, which can be detected to diagnose and monitor prostate cancer. Moreover, increases in serum PSA following local and systemic treatments are highly correlated with tumor recurrence and progression, and this association has further established PSA as a clinically important biomarker. The expression of PSA is mainly induced by androgens and regulated by the androgen receptor (AR) at the transcriptional level. Extensive research on the regulation of PSA gene expression has provided significant information about the function of AR, which is a crucial transcription factor involved in all phases of prostate cancer. Still, the molecular mechanism(s) by which the transcription of the PSA gene escapes regulation in advanced prostate cancer has yet to be clearly defined. Accumulating evidence suggests that a number of processes including androgen-independent activation of AR are involved. Lacking an effective treatment, advanced prostate cancer is almost invariably fatal, which highlights the importance of elucidating mechanisms of tumor progression. Insights into AR activity at the PSA gene could be extended to transcriptional regulation of other AR target genes, which may be crucial in discerning prostate cancer progression. Ultimately, our improved understanding of AR-regulated PSA expression could aid in developing viable therapies in treating and/or preventing advanced prostate cancer. (C) 2004 Wiley-Liss, Inc.