Dysregulation of β-catenin by hepatitis B virus X protein in HBV-infected human hepatocellular carcinomas.
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.
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, 200438, China.
Lei
L
Chen
Liang
L
Hu
Liang
L
Li
Yuan
Y
Liu
Qian-Qian
QQ
Tu
Yan-Xin
YX
Chang
He-Xin
HX
Yan
Meng-Chao
MC
Wu
Hong-Yang
HY
Wang
D022005:Adherens Junctions / Q000473:pathology; D015152:Blotting, Northern; D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000821:virology*; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D015967:Gene Expression Regulation, Viral; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000503:physiopathology* / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000821:virology*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D054334:Viral Regulatory and Accessory Proteins; D051176:beta Catenin / Q000096:biosynthesis*
C495270:CTNNB1 protein, human; D015820:Cadherins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; D051176:beta Catenin; C057628:hepatitis B virus X protein