[Androgen receptor gene mutations in prostate cancer]

Androgens are required for the development of normal prostate and prostate cancer, through their action via the androgen receptor (AR). Although prostate cancer is potentially curable in the early stages by radical prostatectomy, androgen ablation is standard treatment for metastatic prostate cancer. Metastatic prostate cancer is incurable despite temporary remission commonly achieved by androgen ablation therapy. To investigate the mechanism for the development of human prostate cancer, examination was made of AR gene mutations.

Thirty-two samples including 29 primary prostate cancers and 3 metastatic lymph nodes were examined from exons B to H of the AR gene by polymerase chain reaction of single-strand conformation polymorphism (PCR-SSCP) and direct-sequencing analysis. Three metastatic lymph nodes were removed from non-hormone treated stage D1 patients by radical prostatectomy. Six of 11 stage D2 patients were hormone-independent stage following androgen ablation therapy.

One of 29 (3.4%) primary prostate cancers and 1 of 6 (16.7%) hormone-independent stage D2 patients showed the AR mutation. This AR mutation is a G to A transition at nucleotide 2677 that leads to substitution of glutamine (CAG) for the wild type arginine (CGG) at codon 629. The serum prostate specific antigen level of the patients increased to 480 ng/ml. Drugs for hormone therapy and duration of treatment had the same effects on the remaining 5 hormone-independent patients. No mutation was found in the other 28 primary prostate cancer or 3 metastatic lymph node samples.

The AR mutation may possibly be involved in the development of prostate cancer from the androgen-dependent to -independent stage during androgen ablation therapy.