Methylation and Androgen Receptor Gene Expression in Prostate

• Main Authors: Pei-I Lin, 林珮伊
• Other Authors: Da-Chang Chu
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/44032027308605095089

碩士 === 長庚大學 === 醫學生物技術研究所 === 92 === Abstract Prostate cancer is the most frequently diagnosed malignancy and second leading cause of male cancer death in the USA. At first, growth of prostate cancer cells is androgen-dependent. According to previous reports, 20-30% hormone refectory prostate cancer (HRPC) would be characterized by loss of androgen receptor (AR) expression. Methylation of CpG dinucleotides in gene promoter region, one of the mechanisms regulating gene expression, usually resulted in diminished or abolished gene expression.This study used sodium bisulfite treatment combined DNA sequencing to investigate the correlation of methylation and AR gene expression. In human cell lines, the expression of AR mRNA is higher in LNCaP than PC-3, BPH and PZ. No AR mRNA expression was found in CA and DU145 cells. In the protein level, both western blot and immunohistochemistry (IHC) staining revealed that only LNCaP cells expressed AR protein. In TRAMP mice, we observed higher AR expression than in normal C57BL/6 mice. However, there was no significant variation of AR mRNA expression between different stages of cancer. IHC data demonstrated that AR expressed in various pathological stages. Besides, we had detected higher methylation status of AR promoter CpG sites in DU145 (54%) and CA (21%). And the methylation percentages of PZ, BPH, PC-3, and LNCaP cells were 15%, 6%, 10%, and 4%, respectively. In TRAMP mice, we found no methylation in the AR promoter region in all samples. In conclusion, methylation of AR gene promoter would affect AR expression in human prostate cancer cell lines but not in TRAMP animal model.