The role of MAPK-ERK pathway in 67-kDa laminin receptor-induced FasL expression in human cholangiocarcinoma cells.

Digestive Diseases and Sciences
Shi-Gang DuanShu-Guang Wang

Abstract

Cancer cells are thought to possess immune evasion properties due to FasL overexpression in many types of human tumors. In the present study, we set out to investigate the role of MAPK-ERK pathway in 67-kDa laminin receptor induced FasL expression and FasL-mediated apoptosis in human cholangiocarcinoma cells. The expression of FasL and its promoter activity in cultured cholangiocarcinoma cells were examined after treatment with laminin or transfection with plasmids containing siRNA targeted to 67-kDa laminin receptor. The effects of MAPK-ERK cascade inhibitor and c-Myc inhibition by siRNA on 67-kDa laminin receptor-induced FasL expression were determined. Apoptosis assay was performed to analyze the apoptosis of lymphocytes cocultured with cholangiocarcinoma cells treated with or without MAPK-ERK cascade inhibitor. Our results revealed that the specific MAPK-ERK cascade inhibitor, PD98059, significantly attenuated phosphorylation of c-Myc on Ser-62 and FasL upregulation in QBC-939 cells and these cells showed decreased cytotoxicity against Fas-sensitive Jurkat T cells. A luciferase reporter assay revealed that FasL promoter activity was significantly reduced in cells treated with PD98059 or transfected with c-Myc siRNA. Based o...Continue Reading

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Citations

May 6, 2014·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Jing XuShuguang Wang
Oct 7, 2014·Breast Cancer Research and Treatment·Honghai HongGuoquan Gao
Jan 15, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Feng TianShuguang Wang
Jun 25, 2015·Carcinogenesis·Kannan Badri NarayananHyun Ho Park
Apr 26, 2016·Transplant Immunology·Fatina I FadelEman H Thabet
Nov 15, 2019·Expert Opinion on Therapeutic Patents·Leila VaniaStefan F T Weiss
Mar 8, 2020·International Journal of Molecular Sciences·Antaripa BhattacharyaDaniela Sarnataro

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