Methylation-mediated Silencing of TMS1 in Pancreatic Cancer and its Potential Contribution to Chemosensitivity

Background: Resistance to chemotherapeutic agents, resulting in part from epigenetic silencing of proapoptotic genes, is one of the causes of treatment failure of pancreatic cancer. We examined whether epigenetic silencing of target of methylation induced silencing 1 (TMS1) contributes to resistance to chemotherapy in pancreatic cancer. Materials and Methods: Methylation analysis was performed by methylation-specific PCR (MS-PCR) and gene expression was analyzed by quantitative reverse transcriptase PCR (qRT-PCR). MIA PaCa-2 cells were transfected with pCMV6-XL5/TMS1 plasmid and the effect of TMS1 expression on sensitivity to gemcitabine and docetaxel was determined. Cell viability was measured using Cell Titer Blue assay. Results: TMS1 expression was repressed in MIA PaCa-2 cells by DNA methylation. Up-regulation of TMS1 by recombinant gene expression in MIA PaCa-2 cells or by pretreatment of these cells with 5-azacytidine resulted in enhanced sensitivity to gemcitabine and docetaxel. Conclusion: Our results suggest that TMS1 is a potential therapeutic target in pancreatic cancer.