Abstract
Recent reports have suggested that Dual Oxidases (DUOX1 & DUOX2) are epigenetically silenced in non-small cell lung, hepatocellular, and breast cancers and may act as tumor suppressor genes. These NADPH Oxidase (NOX) family members are responsible for the production of hydrogen peroxide (H2O2) on the extracellular surface of cells. However, epigenetic silencing of DUOX in pancreatic ductal adenocarcinoma has never been studied. In vitro, we observed that DUOX1 and DUOX2 mRNA and protein expression was significantly reduced in all PDAC cell lines tested when compared to a non-tumorigenic pancreatic ductal epithelial cell line. In addition, 5-azacitidine, an inhibitor of DNA methyltransferases, induced the expression of DUOX1 and DUOX2 (5-20 fold, P 50%) in expression of DUOX 1 and 2 when compared to adjacent, normal pancreas. Overall, these results suggest that DUOX expression is epigenetically silenced and may present as a novel therapeutic target for the treatment of pancreatic ductal adenocarcinoma.
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