乙肝病毒X蛋白对人肝细胞内β-catenin定位及转录活性的影响  

Effect of hepatitis B virus X protein on nuclear localization and transcription of β-catenin in human liver cell

作　　者：丁浩[1] 何柳兴[2] 冯涛[3] 

机构地区：[1]重庆医药高等专科学校内科教研室,重庆402260 [2]成都大学医护学院生物化学教研室,四川成都610015 [3]重庆医科大学医学与肿瘤研究中心,重庆400016

出　　处：《基础医学与临床》2009年第5期475-478,共4页Basic and Clinical Medicine

基　　金：国家自然科学基金(30771925)

摘　　要：目的研究HBx对Wnt/Wingless信号传导通路中主要信号分子β-catenin的影响,探讨HBV相关性HCC的发生机制。方法Ad-HBx转染人肝细胞系L02细胞,免疫细胞化学和Luciferase检测细胞中β-catenin细胞定位及活性变化。结果免疫细胞化学:转染重组HBx腺病毒前L02细胞中β-catenin仅在细胞质有少量表达,转染后胞质表达明显增强,并出现胞核的大量积聚;Luciferase检测:实验组TOP荧光素酶活性与对照组及空白组相比明显增强,为阴性对照的11倍(P<0.05),Ad-HBx感染后24 h和36 h的TOP荧光素酶活性无显著差异。结论Ad-HBx重组腺病毒在体外能有效转染人肝细胞系L02细胞,受感染细胞能有效表达HBx蛋白,HBx影响了人肝细胞系L02细胞中β-catenin的细胞定位及转录活性。Objective To investigate the interaction between HBx protein and β-catenin for exploring molecular mechanism in HBV-associated hepatocellular carcinoma. Methods Iimmunocytochemistry and Luciferase Assay were used to detect the endocellular location and transcriptional activity of β-catenin in normal liver cell line L02 infected by Ad-HBx. Results Immunocytochemistry ： there was markedly increased expression of β-catenin in cytoplasm and nucleus. Luciferase Assay： Ad-HBx led to a significant increase of TCF-4-dependent transcription, the TOP count of Ad-GFP and Ad-HBx-GFP was 1.4 fold and 11 fold as compared to the negative control respectively （P 〈 0. 05）. Conclusion There is the expression of HBx protein in human normal liver cell line （L02） with infected Ad-HBx. This result suggests that ectopic expression of HBx leads to accumulation of β-catenin in the cytoplasm and subsequent nuclear localization and increases TCF-4-dependent transcription in L02 cells. HBx protein is essential for the activation of wnt/β-catenin signaling by increasing the expression of β-catenin in normal liver cells.

关 键 词：WNT/Β-CATENIN信号转导通路 HBX Β-CATENIN 腺病毒载体 肝细胞肝癌 

分 类 号：R512.6[医药卫生—内科学] R735.7[医药卫生—临床医学]