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Hepatitis C virus core protein induces malignant transformation of biliary epithelial cells by activating nuclear factor‐κB pathway
Author(s) -
Li ZhiHua,
Tang QiBin,
Wang Jie,
Zhou Ling,
Huang Wenlin,
Liu RanYi,
Chen RuFu
Publication year - 2010
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2009.06201.x
Subject(s) - transfection , microbiology and biotechnology , telomerase reverse transcriptase , hepatitis b virus , immunoprecipitation , viral transformation , hepatitis c virus , phosphorylation , hep g2 , blot , virology , biology , cell culture , virus , telomerase , antibody , gene , immunology , biochemistry , genetics
Background and Aim: In an earlier study, we found that hepatitis C virus core protein, HCV‐C, participated in the malignant transformation of HCV‐C transfected normal human biliary epithelial (hBE) cells by activating telomerase. Here we further investigated the signaling of the malignant transformation. Methods: Reverse transcription‐polymerase chain reaction (RT‐PCR), western blotting and immunoprecipitation were used to analyze the expression of HCV‐C, human telomerase reverse transcriptase (hTERT), nuclear factor‐κB (NF‐κB) and NF‐κB inhibitor alpha (IκBα) genes and the phosphorylation level of IκBα protein. Electrophoretic mobility shift assays (EMSA) and NF‐κB‐linked luciferase reporter assays were carried out to measure NF‐κB activity. Results: The expression of HCV‐C and hTERT was detected only in HCV‐C‐transfected hBE (hBE‐HCV‐C) cells but not in vector‐transfected or parental hBE cells. More NF‐κB protein accumulated in nuclear extracts of hBE‐HCV‐C cells rather than in those of control cells, though total NF‐κB protein level showed no difference among these cells. DNA binding activity of NF‐κB and the NF‐κB‐linked luciferase activity were much higher in HCV‐C‐transfected hBE cells than those in vector‐ or non‐transfected hBE cells. In addition, the IκBα phosphorylation level, but not the IκBα mRNA or protein levels, was increased after HCV‐C transfection. Conclusions: Hepatitis C virus core protein activates NF‐κB pathway in hBE cells by increasing the phosphorylation of IκBα. The pathway may be responsible for HCV‐C‐induced malignant transformation of hBE cells.