Abstract
To investigate the mechanism for the development of human prostate cancer, examination was made of structural abnormality of the androgen receptor (AR) gene in 29 human prostate cancer. AR gene mutations from exons A to H were examined by PCR-SSCP and microsatellite instability analysis using (CAG)n and (GGN)n polymorphic markers in AR gene exon A. A point mutation was found in the exon D hormone-binding domain of AR leading to substitution of glutamine (GAG) for wild-type arginine (CGG) at codon 629 in 1 (3.4%) hormone-independent stage D2 patient. Microsatellite instability was detected in 5 of the 27 (18.5%) patients, 1 of 6 (16.7%) hormone-independent stage D2 and 4 of 21 (19.0%) hormone-dependent and non-treated prostate cancer patients. AR mutations may possibly be involved in the transition from androgen-dependent to independent stages during androgen ablation therapy.
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