Zinc fingers and homeoboxes 2 involves in oncogenic activation of glypican 3 in human hepatocellular carcinoma

作     者：Luan Fang~(1,2),Yue Xuetian~1,Liu Peng~1,Liu Jun~3,Liang Xiaohong~1,Shi Wei~1,Gao Lifen~1,Spear Brett~4,Ma Chunhong~1 1.Key Laboratory for Experimental Teratology of Ministry of Education and Institute of Immunology,Shandong University School of Medicine,44 Wenhua Xi Road,Jinan,Shandong,250012 P.R.China. 2.Department of Clinical laboratory,Provincial Hospital affiliated to Shandong University,324 Jingwu Road,Jinan,Shandong,250021 P.R.China. 3.Department of Surgery,Provincial Hospital affiliated to Shandong University,324 Jingwu Road,Jinan,Shandong,250021 P.R.China. 4.Department of Microbiology,Immunology,&Molecular Genetics and Markey Cancer Center,University of Kentucky College of Medicine,Lexington,KY,USA. 

会议名称：《2012全国临床微生物与感染免疫学术研讨会》

会议日期：2012年

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

关 键 词：ZHX2 GPC3 HCC Negative regulation 

摘      要：Background & Aims Glypican 3(GPC3) expresses abundantly in fetal liver and is silent in normal adult liver but becomes reactivated in hepatocellular carcinoma(HCC).And recently GPC3 has been the focus of particular interests because of its potential usefulness as a specific marker for *** study the mechanisms regulating the reactivation of GPC3 in HCC appears to be clinically ***-fingers and homeoboxes 2(ZHX2) are ubiquitously expressed and localized to the nuclei of cells,and appear to function as transcriptional repressors. Previous data have shown that ZHX2 protein is involved in postnatal repression of GPC3 ***,we hypothesized ZHX2 might regulate GPC3 expression in HCC. Methods ZHX2 and GPC3 expression were analyzed by RT-PCR,Western blot and immunohistochemistry to evaluate the correlation of ZHX2 and GPC3 *** effects of ZHX2 overexpressed and sh-RNA mediated ZHX2 knockdown in different HCC cell lines were examined in regard to GPC3 *** assay of ZHX2 in HCC and cytoplasmic/nuclear ZHX2 staining in HCC and adjacent non-tumor sections were carried out to reveal the mechanism of GPC3 reactivation in *** reporter assays and chromatin immunoprecipitation were used to measure effects of ZHX2 on GPC3 promoter. RGSUltS Inverse correlation of ZHX2 and GPC3 expression was demonstrated not only in cultured liver cell lines but also in HCC *** of ZHX2 inHepG2,Hep3B and HepG2.2.15 cells,which express lower endogenous ZHX2,significantly decreases GPC3 *** contrast,ZHX2 knockdown increases GPC3 levels in SMMC7721 and *** these results represent the first direct evidence that ZHX2 represses GPC3 expression in *** assay of ZHX2 inHCC and cytoplasmic/nuclear ZHX2 staining in HCC and adjacent non-tumor sections reveal that decreased nuclear ZHX2 levels in HCC tissues is responsible for GPC3 reactivation. Co-transfections of ZHX2 and GPC3-luciferase reporter genes demon