Malignant transformation of the cultured human hepatocytes induced by hepatitis C virus core protein

Liver Int. 2005 Feb;25(1):141-7. doi: 10.1111/j.1478-3231.2005.0999.x.

Abstract

Background/aim: Hepatitis C virus core protein (HCV-C) has been known to play an important role in hepatocarcinogenesis. But, up to now there is no certain evidence in pathomorphology directly supporting this standpoint. In this study, a human hepatocytes model expressing HCV-C was established for investigating the influence of HCV-C on hepatocytes biological properties.

Methods: The HCV-C expression plasmid, PcDNA3-C, was transfected into Chang-liver cells to establish HCV-C expressing cells. Proliferation rate and variation index of DNA content of these cells were measured by MTT and FCM. The malignant transformation of these cells was observed by electron microscope. Furthermore, these cells were subcutaneous injected into nude mice to observed their tumor genesis.

Results: Proliferation rate and variation index of DNA content of these cells markedly increased. 10/10 of BALB/c-nu/nu nude mice generated tumors at 3 weeks after subcutaneous inoculation of the HCV-C expressing cells. And, histological structure of the tumors coincided with that of hepatocarcinoma.

Conclusions: The HCV-C may play a key role in hepatocarcinogenesis resulting from HCV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line
  • Cell Proliferation
  • Cell Transformation, Neoplastic*
  • DNA / analysis
  • Hepacivirus / isolation & purification
  • Hepacivirus / physiology*
  • Hepatocytes / pathology*
  • Hepatocytes / ultrastructure
  • Humans
  • Liver Neoplasms, Experimental / etiology
  • Liver Neoplasms, Experimental / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Plasmids
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Viral Core Proteins / genetics
  • Viral Core Proteins / metabolism*

Substances

  • RNA, Messenger
  • Viral Core Proteins
  • DNA