Expression of UDP Glucuronosyltransferases2B15and2B17is 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 ofUGT2B15, UGT2B17,de novomethyltransferases,DNMT3AandDNMT3Bwas 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 ofUGT2B15andUGT2B17over 85% as well as significantly decreased expression ofDNMT3B, but not the expression ofDNMT3A. DNMT3BsiRNA treated LNCaP cells had decreased expression ofUGT2B15andUGT2B17, whileDNMT3AsiRNA treated cells had only moderately decreasedUGT2B15expression. Treatment with DNMT methyltransferase inhibitor, RG108, significantly decreasedUGT2B17expression. 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 theUGT2B15andUGT2B17genes 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.