Correlation between the germline methylation status in ERβ promoter and the risk in prostate cancer: a prospective study.

Familial aggregation of cancer may reflect an overall contribution of inherited genes or a shared mechanism for the manipulation of gene function. DNA methylation in the promoter regions is considered to be a mechanism through which tumor suppressor genes are inhibited, which will lead to tumorigenesis and tumor progression. To evaluate the association between the methylation status in the promoter of estrogen receptor (ER) β,possibly a tumor suppressor gene specific for prostate cancer, and the risk in prostate cancer in a Chinese population, a case-control study that included 56 sporadic prostate cancer cases and 60 healthy controls was conducted. Genomic DNA was extracted from peripheral blood of all the subjects for analyzing the methylation status of the ERβ promoter by methylation-specific PCR, which was verified by bisulfite genomic sequencing PCR. A significant difference was observed in the methylation frequencies of the ERβ promoter between cancer patients (12/56, 21.4%) and healthy controls (5/60, 8.3%). Prostate cancer (PC-3 and DU-145) and prostatic epithelial (RWPE-1) cell lines were treated with various concentrations of the methyltransferase inhibitor 5-Aza-2'-dC. Expression of ERβ was detected at both transcriptional and translational levels. As a result, both mRNA and protein of ERβ were elevated following treatment with increasing concentrations of the demethylating agent. Taken together, our results support the conclusion that abnormal methylation of the ERβ promoter may increase genetic susceptibility to prostate cancer.