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/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 pre-treatment 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.
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/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 pre-treatment 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.
Authors: Sherif G Ahmed; Ahmed Abdelnabi; Casey A Maguire; Mohamed Doha; Jessica E Sagers; Rebecca M Lewis; Alona Muzikansky; Marco Giovannini; Anat Stemmer-Rachamimov; Konstantina M Stankovic; Giulia Fulci; Gary J Brenner Journal: Neuro Oncol Date: 2019-07-11 Impact factor: 12.300
Authors: E R W Knight; E Y Patel; C A Flowers; A J Crowther; J P Ting; C R Miller; T R Gershon; M Deshmukh Journal: Oncogene Date: 2014-01-27 Impact factor: 9.867