Histone deacetylase and DNA methyltransferase in human prostate cancer.
CpG island hypermethylation and chromatin remodeling play important roles in repression of various genes during malignant transformation. We hypothesized that histone deacetylases (HDACs) and DNA methyltransferases (DNMTase) are associated with prostate cancer and we examined the enzyme activity, gene, 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 cell lines compared to benign prostatic hyperplasia (BPH-1) cell line. Treatment of cells with 5-aza-2'-deoxycytidine decreased the activity of HDAC and DNMTase. The mRNA expression of these genes in BPH-1 cells and BPH tissues 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-regulated in prostate cancer compared to BPH, suggesting their roles in inactivation of various genes, by DNA-methylation-induced chromatin-remodeling, in prostate cancer.
Patra
S K
SK
Department of Urology, University of California at San Francisco, San Francisco, California 94121, USA.
Patra
A
A
Dahiya
R
R
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D018899:CpG Islands; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000096:biosynthesis* / Q000235:genetics; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D006655:Histone Deacetylases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D012333:RNA, Messenger; D000077209:Decitabine; D015254:DNA Modification Methylases; D006655:Histone Deacetylases; D001374:Azacitidine