Chen Lei, Hu Liang, Li Liang, Liu Yuan, Tu Qian-Qian, Chang Yan-Xin, Yan He-Xin, Wu Meng-Chao, Wang Hong-Yang
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, 200438, China.
Front Med China. 2010 Dec;4(4):399-411. doi: 10.1007/s11684-010-0170-y. Epub 2010 Nov 23.
β-catenin is a key molecule involved in both cell-cell adhesion and Wnt signaling pathway. In our study, we found that, in the development of hepatocellular carcinoma (HCC), β-catenin was correlated with hepatitis B virus (HBV) X gene encoded protein, which is essential for HBV infectivity and is a potential cofactor in viral carcinogenesis. The expression levels of wild-type β-catenin and E-cadherin were decreased in HepG2 cells expressing hepatitis B virus X protein (HBx), accompanied by destabilization of adherens junction. Reverse transcriptase PCR (RT-PCR), Northern and Western blot showed that reduction of wild-type β-catenin expression involved degradation of the protein. However, RNA interference (RNAi) and luciferase assay indicated that HBx enhanced β-catenin mediated signaling in HepG2 cells. In addition, immunohistochemical and Western blot analysis of β-catenin revealed that a decrease in the β-catenin protein level was found in 58.3% of HBV-related HCCs versus 19.2% of non-HBV-related tumors. Our data suggest that the expression of HBx contributed to the development of HCC, in part, by repressing the wild-type β-catenin expression and enforcing β-catenin-dependent signaling pathway, thus inducing cellular changes leading to acquisition of metastatic and/or proliferation properties.
β-连环蛋白是一种参与细胞间黏附以及Wnt信号通路的关键分子。在我们的研究中，我们发现，在肝细胞癌（HCC）的发生发展过程中，β-连环蛋白与乙型肝炎病毒（HBV）X基因编码蛋白相关，该蛋白对HBV感染至关重要，并且是病毒致癌作用中的一个潜在辅助因子。在表达乙型肝炎病毒X蛋白（HBx）的HepG2细胞中，野生型β-连环蛋白和E-钙黏蛋白的表达水平降低，同时伴有黏附连接的不稳定。逆转录聚合酶链反应（RT-PCR）、Northern印迹和Western印迹显示，野生型β-连环蛋白表达的降低涉及该蛋白的降解。然而，RNA干扰（RNAi）和荧光素酶检测表明，HBx增强了HepG2细胞中β-连环蛋白介导的信号传导。此外，对β-连环蛋白的免疫组织化学和Western印迹分析显示，在58.3%的HBV相关HCC中发现β-连环蛋白水平降低，而在非HBV相关肿瘤中这一比例为19.2%。我们的数据表明，HBx的表达部分通过抑制野生型β-连环蛋白的表达并强化β-连环蛋白依赖性信号通路，从而诱导细胞变化导致获得转移和/或增殖特性，进而促进了HCC的发生发展。
