Abstract
<div>Abstract<p>Calcitriol, a regulator of calcium homeostasis with antitumor properties, is degraded by the product of the <i>CYP24A1</i> gene, which is downregulated in human prostate cancer by unknown mechanisms. We found that <i>CYP24A1</i> expression is inversely correlated with promoter DNA methylation in prostate cancer cell lines. Treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (DAC) activates <i>CYP24A1</i> expression in prostate cancer cells. <i>In vitro</i> methylation of the <i>CYP24A1</i> promoter represses its promoter activity. Furthermore, inhibition of histone deacetylases by trichostatin A (TSA) enhances the expression of <i>CYP24A1</i> in prostate cancer cells. Quantitative chromatin immunoprecipitation-PCR (ChIP-qPCR) reveals that specific histone modifications are associated with the <i>CYP24A1</i> promoter region. Treatment with TSA increases H3K9ac and H3K4me2 and simultaneously decreases H3K9me2 at the <i>CYP24A1</i> promoter. ChIP-qPCR assay reveals that treatment with DAC and TSA increases the recruitment of vitamin D receptor to the <i>CYP24A1</i> promoter. Reverse transcriptase-PCR analysis of paired human prostate samples revealed that <i>CYP24A1</i> expression is downregulated in prostate malignant lesions compared with adjacent histologically benign lesions. Bisulfite pyrosequencing shows that <i>CYP24A1</i> gene is hypermethylated in malignant lesions compared with matched benign lesions. Our findings indicate that repression of <i>CYP24A1</i> gene expression in human prostate cancer cells is mediated in part by promoter DNA methylation and repressive histone modifications. Cancer Res; 70(14); 5953–62. ©2010 AACR.</p></div>
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call