Androgen Receptor Coregulators and Their Role in Prostate Cancer

The limiting factor in the survival of a patient with prostate cancer is the rate of progression to the noncurable androgen-independent (AI) stage of disease. The androgen receptor (AR) is a critical regulator of prostate cancer development and is involved in AI progression. Coregulators are proteins that interact directly with AR to enhance (coactivators) or reduce (corepressors) its transcriptional activity. Currently, over 165 AR coregulators have been discovered. In this chapter, we focus on a subset of the most well-characterized AR coregulators that are associated with prostate cancer. The first part of our review discusses the mechanisms by which classical type I and nonclassical type II AR coactivators/corepressors regulate AR transcriptional activity. The second section focuses on the role of coregulators in prostate cancer, including their expression profile in prostate cancer patients, tumor cell growth effects, and potential as therapeutic targets. In view of their involvement in prostate cancer progression, it is anticipated that further study of AR coregulators will provide more treatment options for increasing survival of patients with AI prostate cancer.