Methylation-mediated silencing of TMS1 in pancreatic cancer and its potential contribution to chemosensitivity

Kavitha Ramachandran, Heather Miller, Edna Gordian, Caio Max S Rocha Lima, Rakesh Singal

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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 languageEnglish (US)
Pages (from-to)3919-3925
Number of pages7
JournalAnticancer research
Issue number10
StatePublished - Oct 1 2010


  • Chemotherapy
  • DNA methylation
  • Epigenetics
  • Pancreatic cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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