The androgen receptor gene and its influence on the development and progression of prostate cancer

Prostate adenocarcinoma has the highest incidence of any malignancy and is the second leading cause of cancer-related deaths in men in industrialized countries. The development and progression of prostate cancer are dependent on testosterone and dihydrotestosterone; the androgen receptor is the vehi cle through which these androgens exert their regulation on prostate cellul ar proliferation and differentiation. As a result, much effort has been dev oted to elucidating the role of the androgen receptor in prostate cancer. T he CAG and GGN trinucleotide repeats in exon 1 of the androgen receptor gen e have been linked to prostate cancer risk and progression in some studies. Also, androgen receptor gene amplification may be a mechanism of prostate cancer cell adaptation to hormonal therapy. In addition, androgen receptor somatic mutations can result in receptors that have altered binding specifi city when compared with wild-type receptors and heightened affinity for hor mones other than testosterone and dihydrotestosterone. Gene amplification a nd somatic mutations, coupled with the fact that various growth factors hav e been shown to stimulate androgen receptor activity independently of andro gens, may enable prostate cancer cells to grow despite testicular-androgen ablation. Unfortunately, current medical therapy for metastatic prostate ca ncer is deficient, hormone-refractory prostate cancer is a major obstacle i n treatment, and, as a result, prostate cancer mortality is still significa nt. Further study of the function of the androgen receptor will offer a bet ter understanding of prostate cancer pathogenesis and progression, aiding t he development of more effective treatments for this disease.