Expression of UDP Glucuronosyltransferases <i>2B15</i> and <i>2B17</i> is associated with methylation status in prostate cancer cells

Studies have suggested that abrogated expression of detoxification enzymes, UGT2B15 and UGT2B17, are associated with prostate tumour risk and progression. We investigated the role of EGF on the expression of these enzymes since it interacts with signalling pathways to also affect prostate tumour progression and is additionally associated with decreased DNA methylation. The expression of <i>UGT2B15, UGT2B17</i>, <i>de novo</i> methyltransferases, <i>DNMT3A</i> and <i>DNMT3B</i> was assessed in prostate cancer cells (LNCaP) treated with EGF, an EGFR inhibitor PD16893, and the methyltransferase inhibitor, 5-azacytidine, respectively. The results showed that EGF treatment decreased levels of expression of all four genes and that their expression was reversed by PD16893. Treatment with 5-azacytidine, markedly decreased expression of <i>UGT2B15</i> and <i>UGT2B17</i> over 85% as well as significantly decreased expression of <i>DNMT3B</i>, but not the expression of <i>DNMT3A. DNMT3B</i> siRNA treated LNCaP cells had decreased expression of <i>UGT2B15</i> and <i>UGT2B17</i>, while <i>DNMT3A</i> siRNA treated cells had only moderately decreased <i>UGT2B15</i> expression. Treatment with DNMT methyltransferase inhibitor, RG108, significantly decreased <i>UGT2B17</i> expression. Additionally, methylation differences between prostate cancer samples and benign prostate samples from an Illumina 450K Methylation Array study were assessed. The results taken together suggest that hypomethylation of the <i>UGT2B15</i> and <i>UGT2B17</i> genes contributes to increased risk of prostate cancer and may provide a putative biomarker or epigenetic target for chemotherapeutics. Mechanistic studies are warranted to determine the role of the methylation marks in prostate cancer.