Epigenetic suppression of the anti-aging gene in human prostate cancer cell lines.

was originally identified as an aging-suppressor gene that causes a human aging-like phenotype when tested in -deficient-mice. Recent evidence suggests that functions as a tumor suppressor by inhibiting signaling. gene silencing, including DNA methylation, has been observed in some human cancers. Aberrant activation of signaling plays a significant role in aging, and its silencing may be related to prostate cancer and other types of cancers. Thus, we investigated whether the expression of the anti-aging gene was associated with epigenetic changes in prostate cancer cell lines. mRNA was detected in the 22Rv1 cell line while it was not detected in DU145 and PC-3 cell lines. The restoration of mRNA in the DU145 and PC-3 cell lines was induced with a DNA methyltransferase inhibitor. Methylation-specific PCR was performed to determine the specific CpG sites in the promoter responsible for expression. In addition, the level of methylation was assessed in each CpG by performing bisulfite sequencing and quantitative pyrosequencing analysis. The results suggested a remarkable inverse relationship between expression and promoter methylation in prostate cancer cell lines.