DNA mismatch repair enzyme activity and gene expression in prostate cancer

Microsatellite instability (MSI) of short repetitive sequences in human chr omosomal DNA can result from defective DNA mismatch repair function in tu m or cells. We hypothesize that DNA mismatch repair (MMR) activity is down-re gulated during prostatic carcinogenesis. To test this hypothesis, MMR activ ities and mismatch repair-related genes were analyzed in five different pro state cancer cell lines. Our results demonstrate that MMR activities were d ecreased 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 mR NA 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 bMSH2 protein expression was low or absent in DU145 and LNCaP cells. This is the first report that demonstrates decre ased MMR activities is associated with low expression of hMLH1, hMSH2 and o ther MMR-related proteins in prostate cancer. (C) 2001 Academic Press.