Androgen-selective gene regulation in the prostate

Androgens are essential for normal prostate growth and function but are also intimately associated with prostate cancer, an important cause of mortality in the ageing male population. The effects of androgens are mediated via a specific androgen receptor (AR) belonging to the nuclear receptor family and acting as a ligand-dependent transcription factor. The AR is built in a modular fashion and composed of a long N-terminal region with transactivation functions, a central DNA-binding domain, an intermediate hinge region and a C-terminal ligand-binding domain with additional transactivation functions. In its inactive form, the AR is complexed to heat-shock proteins, and mainly cytoplasmic. Following activation, the AR enters the nucleus, binds to its cognate DNA response elements as a homodimer and stimulates gene transcription. Various cofactors directly interact with the AR to modulate gene transcription. In addition, cross-talk between the AR and other signalling pathways has been proven for several prostate-expressed genes. Understanding the intricate networks underlying androgen-selective gene regulation represents a formidable challenge but might also offer the chance to identify new drug targets for the treatment of prostate carcinoma.