Background: Resistance to chemotherapeutic agents, resulting in part from epigenetic silencing of pro-apoptotic 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/TMSl 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 MlA 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.
|Original language||English (US)|
|Number of pages||7|
|State||Published - Oct 1 2010|
- DNA methylation
- Pancreatic cancer
ASJC Scopus subject areas
- Cancer Research