Histone deacetylase and DNA methyltransferase in human prostate cancer

CpG island hypermethylation and chromatin remodeling play important roles i n repression of various genes during malignant transformation. We hypothesi zed that histone deacetylases (HDACs) and DNA methyltransferases (DNMTase) are associated with prostate cancer and we examined the enzyme activity, ge ne, and protein expression of HDAC1 and DNMT1 in cell lines and tissues. We found that DNMTase and HDACs activities were two- to threefold higher in c ell lines compared to benign prostatic hyperplasia (BPH-1) cell line. Treat ment of cells with 5-aza-2'-deoxycytidine decreased the activity of HDAC an d DNMTase. The mRNA expression of these genes in BPH-I cells and BPH tissue s was lower than that in prostate cancer cells and tissues. HDAC1 and DNMT1 protein expression was higher in prostate cancer compared to BPH. This is the first report to demonstrate that DNMT1 and HDAC1 levels are up-regulate d in prostate cancer compared to BPH, suggesting their roles in inactivatio n of various genes, by DNA-methylation-induced chromatin-remodeling, in pro state cancer. (C) 2001 Academic Press.