DNA mismatch repair enzyme activity and gene expression in prostate cancer

Microsatellite instability (MSI) of short repetitive sequences in human chromosomal DNA can result from defective DNA mismatch repair function in tumor cells. We hypothesize that DNA mismatch repair (MMR) activity is down-regulated during prostatic carcinogenesis. To test this hypothesis, MMR activities and mismatch repair-related genes were analyzed in five different prostate cancer cell lines. Our results demonstrate that MMR activities were decreased as compared to MMR proficient HeLa cells. Interestingly, LNCaP, PC-3 and DU145 had much lower MMR activities as compared to DUPro and TSUPr1. The MMR-related genes (hMLH1, hPMS1, hPMS2, hMSH2, hMSH3, hMSH6) showed mRNA transcripts in all prostate cancer cell lines. However, Western blotting showed decreased or absent hMLH1 protein expression in PC-3, DU145, DUPro and TSUPr1 cells. Similarly, the hMSH2 protein expression was low or absent in DU145 and LNCaP cells. This is the first report that demonstrates decreased MMR activities is associated with low expression of hMLH1, hMSH2 and other MMR-related proteins in prostate cancer.