Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer

The expression level of the androgen receptor (AR) gene in androgen-depende nt and -independent prostate cancer was determined by using real-time quant itative reverse transcription-PCR assay. Eight benign prostate hyperplasias , 33 untreated and 13 hormone-refractory locally recurrent carcinomas, as w ell as 10 prostate cancer xenografts, were analyzed. All hormone-refractory tumors expressed AR and showed, on average, 6-fold higher expression than androgen-dependent tumors or benign prostate hyperplasias (P < 0.001). Four of 13 (31%) hormone-refractory tumors contained AR gene amplification dete cted by fluorescence irt situ hybridization. Androgen-independent tumors wi th gene amplification expressed, on average, a 2-fold higher level of AR th an the refractory tumors without the gene amplification. Two xenografts (Lu CaP 35 and 69) showed amplification and high-level expression of the AR gen e. These xenografts are the first prostate cancer model systems containing the gene amplification. The findings demonstrate that AR is highly expresse d in androgen-independent prostate cancer, suggesting that the AR signaling pathway is important in the progression of prostate cancer during endocrin e treatment. The two xenografts with the AR gene amplification will enable studies evaluating the functional significance of the amplification and dev elopment of new treatment strategies based on high-level expression of AR.