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Histone deacetylase and DNA methyltransferase in human prostate cancer
1Department of Urology, University of California at San Francisco, San Francisco, California 94121, USA.
Abstract:
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.
Insights
Histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) are elevated in prostate cancer. These enzymes contribute to gene silencing via DNA methylation and chromatin remodeling, driving cancer development.
Area of Science:
- Epigenetics
- Molecular Oncology
Background:
- CpG island hypermethylation and chromatin remodeling are key mechanisms in gene repression during cancer development.
- Histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) are implicated in epigenetic regulation and cancer.
Purpose of the Study:
- To investigate the association of HDACs and DNMTs with prostate cancer.
- To examine the enzyme activity, gene, and protein expression of HDAC1 and DNMT1 in prostate cancer versus benign prostatic hyperplasia (BPH).
Main Methods:
- Enzyme activity assays for HDACs and DNMTs.
- Quantitative analysis of HDAC1 and DNMT1 mRNA and protein expression in cell lines and tissues.
- Treatment with 5-aza-2'-deoxycytidine to assess enzyme activity modulation.
Main Results:
- HDAC and DNMTase activities were 2- to 3-fold higher in prostate cancer cell lines compared to BPH-1 cells.
- 5-aza-2'-deoxycytidine treatment reduced HDAC and DNMTase activities.
- mRNA and protein expression of HDAC1 and DNMT1 were significantly higher in prostate cancer tissues and cells than in BPH tissues and cells.
Conclusions:
- DNMT1 and HDAC1 are upregulated in prostate cancer compared to BPH.
- These epigenetic modifiers likely contribute to gene inactivation through DNA methylation-induced chromatin remodeling in prostate cancer.