1.International Cooperation
Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute,
Second Military Medical University, Shanghai 200438, China; 2.Second Military Medical
University, Shanghai 200438, China; 3.International Cooperation
Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute,
Second Military Medical University, Shanghai 200438, China；National Laboratory
for Oncogenes and Related Genes, Key Lab of Cancer Institute in Renji
Hospital, Shanghai Jiao-Tong University, Shanghai 200441, China;
Abstract：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.
. Dysregulation of β-catenin by hepatitis
B virus X protein in HBV-infected human hepatocellular carcinomas[J]. Front. Med., 2010, 4(4): 399-411.
Lei CHEN, Liang HU, Liang LI, Yuan LIU, Qian-Qian TU, Yan-Xin CHANG, He-Xin YAN, Meng-Chao WU, Hong-Yang WANG, . Dysregulation of β-catenin by hepatitis
B virus X protein in HBV-infected human hepatocellular carcinomas. Front. Med., 2010, 4(4): 399-411.
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