Gli-1在缺氧诱导乳腺癌MDA-MB-231细胞上皮-间质转分化中的重要作用  

The important role of Gli-1 in hypoxia-induced epithelial-mesenchymal transition of breast cancer cell line MDA-MB-231

作　　者：李徐奇[1] 雷建军[2] 徐勤鸿[2] 段万星[2] 盛薇[1] 王康[1] 魏光兵[1] 

机构地区：[1]西安交通大学医学院第一附属医院普通外科,陕西西安710061 [2]西安交通大学医学院第一附属医院肝胆外科,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2014年第6期800-804,819,共6页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.81201824);中央高校基本科研业务费专项资金资助项目(No.2013jdhz33)~~

摘　　要：目的探讨Gli-1在缺氧诱导乳腺癌MDA-MB-231细胞上皮-间质转分化(EMT)及侵袭中的重要作用。方法通过缺氧培养乳腺癌MDA-MB-231细胞,以常氧培养作为对照。Transwell小室侵袭试验检测各组MDAMB-231细胞的侵袭能力;Western blot检测HIF-1α、Gli-1、E-Cadherin和vimentin蛋白的表达水平。通过shRNA稳定转染乳腺癌细胞,再次通过Transwell小室侵袭试验检测缺氧对乳腺癌细胞侵袭能力的影响,Western blot检测HIF-1α、Gli-1、E-Cadherin和vimentin蛋白的表达水平。结果缺氧可明显诱导乳腺癌MDA-MB-231细胞侵袭,并上调HIF-1α、Gli-1和vimentin蛋白,下调E-cadherin蛋白。靶向沉默Gli-1基因后,缺氧失去了对乳腺癌细胞侵袭和EMT的诱导作用。结论缺氧通过上调Gli-1表达活化Hedgehog通路,诱导乳腺癌细胞侵袭及EMT过程。Objective To investigate the important role of Gli-1 in hypoxia-induced epithelial-mesenchymal transition of breast cancer cell line MDA-MB-231. Methods For the present study, breast cancer cell line MDA- MB-231 was cultured under normoxic or hypoxic condition. Then, the shRNA of Gli-1 was stably transfected into MDA-MB-231 cells. Invasion of MDA-MB-231 was detected by the Transwell assay. The expressions of HIF-1α, Gli-1, E-Cadherin and vimentin proteins were determined by Western blot. Results Hypoxia significantly induced the invasion of MDA-MB-231 cells, upregulated the expressions of HIF-1α, Gli-1 and vimentin proteins, and downregulated the expression of E-Cadherin protein. Furthermore, knocking down Gli-1 obviously abrogated hypoxia-induced epithelial-mesenchymal transition and enhanced invasion of MDA-MB-231 cells. Gonclusion Hypoxia induces epithelial-mesenchymal transition and enhances invasion of breast carcinoma cells via strengthening Gli-1 expression and activation of Hedgehog pathway.

关 键 词：乳腺癌 侵袭 上皮-间质转分化 缺氧 Gli-1 HEDGEHOG通路 

分 类 号：R737.9[医药卫生—肿瘤]