Tumor-specific loss of human kallikrein 10 (KLK10/NES-1) by CpG island hypermethylation in breast, ovarian and prostate cancers.

摘要

The human kallikrein 10 (KLK10)/normal epithelial cell-specific-1 (NES-1) gene is highly expressed in normal mammary, ovary and prostate cells, but its expression is dramatically decreased in cancer. We have examined the role of CpG island hypermethylation in the tumor-specific loss of KLK10 expression within breast, ovarian and prostate cancers. We treated cancer cells with the demethylating agent 5-aza-2′-deoxycytidine, and monitored for changes in KLK10 mRNA and hK10 protein expression. Up-regulation of KLK10 mRNA levels was observed through the reverse transcriptase polymerase chain reaction (RT-PCR), which was accompanied by an increase in hK10 protein concentration. Genomic sequencing of sodium bisulfite-treated DNA demonstrated that CpG sites within the KLK10 gene were highly methylated. The data suggests that CpG island hypermethylation is one factor that may be implicated in the down-regulation of kallikrein 10 expression in a subset of breast, ovarian and prostate cancer cells, however, other mechanisms seem to be implicated.