1. The MRTF-A/B function as oncogenes in pancreatic cancer.
- Author
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Song Z, Liu Z, Sun J, Sun FL, Li CZ, Sun JZ, and Xu LY
- Subjects
- Animals, Cell Line, Tumor, Deoxycytidine analogs & derivatives, Deoxycytidine pharmacology, Drug Resistance, Neoplasm, Epithelial-Mesenchymal Transition, Humans, Mice, Neoplasm Transplantation, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms pathology, Trans-Activators metabolism, Transcription Factors metabolism, Gemcitabine, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms genetics, Trans-Activators genetics, Transcription Factors genetics
- Abstract
Despite evidence that MRTF-A/B, co-activators of serum response factor (SRF), promotes tumor cell invasion and metastasis in cancer, there are no studies describing MRTF-A/B in pancreatic cancer. To clarify involvement of MRTF-A/B expression in pancreatic cancer, we used quantitative reverse transcription-polymerase chain reaction and western blot analysis to detect MRTF-A/B in pancreatic cancer, intraductal papillary mucinous neoplasm (IPMN) and non-neoplastic pancreata. MRTF-A/B expression differs significantly between cancer and non-neoplastic tissues as well as between non-neoplastic tissues and IPMN bulk tissues. Next, we studied the roles of MRTF-A/B in vitro. Overexpression of MRTF-A/B promoted epithelial-mesenchymal transition (EMT) and generated stem cell-like cells in normal pancreatic cells. We performed quantitative reverse transcription-polymerase chain reaction to detect the level of MRTF-A/B in 19 pancreatic cancer cell lines. We found that their expression was associated with gemcitabine resistance. Like in normal pancreatic cells, MRTF-A/B also promoted EMT and promoted formation of stem cell-like cells in pancreatic cancer and they could regulate microRNA expression associated with EMT and CICs. Finally, to further demonstrate the roles of MRTF-A/B in vivo, we performed nude mouse model of s.c. xenograft and found that overexpression of MRTF-A and MRTF-B promoted pancreatic cancer growth. Elucidating the roles of MRTF-A/B will help us to further understand molecular basis of the disease and offer new gene targets for effective therapies.
- Published
- 2016
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