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Dysregulation of β-catenin by hepatitis B virus X protein in HBV-infected human hepatocellular carcinomas

Frontiers of Medicine in China volume 4, pages 399–411 (2010)Cite this article

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.

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Affiliations

  1. International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, 200438, China

    Lei Chen, Liang Hu, Liang Li, Yuan Liu, Qian-Qian Tu, Yan-Xin Chang, He-Xin Yan & Hong-Yang Wang

  2. Second Military Medical University, Shanghai, 200438, China

    Meng-Chao Wu

  3. National Laboratory for Oncogenes and Related Genes, Key Lab of Cancer Institute in Renji Hospital, Shanghai Jiao-Tong University, Shanghai, 200441, China

    Hong-Yang Wang

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  1. Lei Chen
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  2. Liang Hu
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  4. Yuan Liu
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  7. He-Xin Yan
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Correspondence to Hong-Yang Wang.

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Both authors contributed equally to this work.

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Chen, L., Hu, L., Li, L. et al. Dysregulation of β-catenin by hepatitis B virus X protein in HBV-infected human hepatocellular carcinomas. Front. Med. China 4, 399–411 (2010). https://doi.org/10.1007/s11684-010-0170-y

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  • DOI: https://doi.org/10.1007/s11684-010-0170-y

Keywords

  • hepatocellular carcinoma
  • hepatitis B virus X protein
  • β-catenin
  • cell adhesion
  • E-cadherin
  • transcriptional activation