Implication of androgen receptor gene methylation in transformation of hormone-resistance in prostate carcinoma / 中华泌尿外科杂志

ABSTRACT

Objective To study the mechanisms underlying this loss of AR expression in rat prostate cancer. Methods The methylation status of the AR gene promoter region in rat prostate cancer and cell lines (PLS10,20,and 30) was investigated by Southern blotting,methylation-specific polymerase chain reaction,and methylation-sensitive single-strand conformation analysis (MS-SSQA). Results AR mRNA expression was not detected in any of the rat prostate cancers or cancer cell lines tested by Northern blot analysis. Higher levels of methylated CpGs were observed in PLS20 than that in PLS10 or 30. Demethylation treatment by 5-aza-2’-deoxycytidine restored AR mRNA expression in PLS20.The CpGs was suggested to be responsible for AR expression in rat prostate cancer,and found to be located-9 and-1 nucleotides upstream of the transcriptional initiation site.All of the examined rat prostate and seminal vesicle cancers demonstrated hypermethylation at these CpG sites. Conclusions These data clearly demonstrate that aberrant hypermethylation in the AR promoter region may play a critical role in AR expression in rat prostate cancers.Loss of AR expression might result in development of hormone-resistant prostate carcinoma.