The MRTF-A/B function as oncogenes in pancreatic cancer.
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.
Department of Hepatobiliary and Pancreatic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
Zhao
Z
Song
Department of Hepatobiliary and Pancreatic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
Zhao
Z
Liu
Department of Radiology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
Jing
J
Sun
Department of Hepatobiliary and Pancreatic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
Feng-Lei
FL
Sun
Department of Hepatobiliary and Pancreatic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
Chuan-Zhi
CZ
Li
Department of Hepatobiliary and Pancreatic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
Jiu-Zheng
JZ
Sun
Department of Hepatobiliary and Pancreatic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
Li-You
LY
Xu
D000818:Animals; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000093542:Gemcitabine
C431575:MRTFA protein, human; C478036:MRTFB protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D003841:Deoxycytidine; D000093542:Gemcitabine