Hepatitis C virus core protein induces malignant transformation of biliary epithelial cells by activating nuclear factor-kappaB pathway

J Gastroenterol Hepatol. 2010 Jul;25(7):1315-20. doi: 10.1111/j.1440-1746.2009.06201.x.


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-kappaB (NF-kappaB) and NF-kappaB inhibitor alpha (IkappaBalpha) genes and the phosphorylation level of IkappaBalpha protein. Electrophoretic mobility shift assays (EMSA) and NF-kappaB-linked luciferase reporter assays were carried out to measure NF-kappaB 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-kappaB protein accumulated in nuclear extracts of hBE-HCV-C cells rather than in those of control cells, though total NF-kappaB protein level showed no difference among these cells. DNA binding activity of NF-kappaB and the NF-kappaB-linked luciferase activity were much higher in HCV-C-transfected hBE cells than those in vector- or non-transfected hBE cells. In addition, the IkappaBalpha phosphorylation level, but not the IkappaBalpha mRNA or protein levels, was increased after HCV-C transfection.

Conclusions: Hepatitis C virus core protein activates NF-kappaB pathway in hBE cells by increasing the phosphorylation of IkappaBalpha. The pathway may be responsible for HCV-C-induced malignant transformation of hBE cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biliary Tract / metabolism*
  • Binding Sites
  • Blotting, Western
  • Cell Line
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Viral* / genetics
  • DNA / metabolism
  • Electrophoretic Mobility Shift Assay
  • Epithelial Cells / metabolism*
  • Genes, Reporter
  • Humans
  • I-kappa B Proteins / metabolism
  • Immunoprecipitation
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • Telomerase / metabolism
  • Time Factors
  • Transcription, Genetic
  • Transfection
  • Viral Core Proteins / genetics
  • Viral Core Proteins / metabolism*


  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Viral Core Proteins
  • nucleocapsid protein, Hepatitis C virus
  • NF-KappaB Inhibitor alpha
  • DNA
  • TERT protein, human
  • Telomerase