Hypoxia-mediated up-regulation of MGr1-Ag/37LRP in gastric cancers occurs via hypoxia-inducible-factor 1-dependent mechanism and contributes to drug resistance

International Journal of Cancer. Journal International Du Cancer
Lili LiuD Fan

Abstract

Our previous study demonstrated hypoxia-inducible factor-1(HIF-1) could prompt multidrug resistance (MDR) phenotype and MGr1-Ag/37LRP, a novel drug-resistance protein was reported by our labortary, associated with multidrug resistance in gastric cancer. Given this association, we hypothesized that MGr1-Ag/37LRP contributed to HIF-1-dependent hypoxia-induced MDR phenotype. Initial experiments revealed that blocking MGr1-Ag/37LRP expression by siRNA in gastric cancer cells effectively reversed multidrug resistance phenotype induced by hypoxia. Subsequent analysis of MGr1-Ag/37LRP mRNA and protein in gastric cancer cells revealed a time-dependent manner increase with hypoxia. While the up-regulation of MGr1-Ag/37LRP was abolished by HIF-1 inhibition with siRNA. Studies using luciferase promoter constructs revealed a significant increase in activity in cells subject to hypoxia and such hypoxia inducibility was lost in cells co-transfected siRNA targeting HIF-1. Analysis of the MGr1-Ag/37LRP promoter revealed several potential binding sites for HIF-1. Electrophoretic mobility shift assay and chromatin immunoprecipitation demonstrated a functional HIF-1 binding site within MGr1-Ag/37LRP gene regulatory sequence located at -16 to -11 ...Continue Reading

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Citations

Jan 26, 2013·The Journal of Clinical Investigation·Motofumi KumazoeHirofumi Tachibana
Dec 10, 2009·International Journal of Cancer. Journal International Du Cancer·Lili LiuDaiming Fan
Apr 8, 2014·International Journal of Cancer. Journal International Du Cancer·Lin ZhouKaichun Wu
Oct 18, 2016·Cell Biochemistry and Function·Hongjie WuBaozhong Shi
Jun 18, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yongan ZhouLili Liu
Aug 13, 2015·Molecular Cancer Therapeutics·Shuntaro TsukamotoHirofumi Tachibana
Jan 12, 2021·Journal of Experimental & Clinical Cancer Research : CR·Muhlis AkmanChiara Riganti
Nov 26, 2020·Drug Design, Development and Therapy·Ruo-Lan LiChun-Jie Wu
Dec 10, 2020·Cells·Dimas Carolina BelisarioChiara Riganti
Mar 17, 2020·Biochemical and Biophysical Research Communications·Motofumi KumazoeHirofumi Tachibana

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