Reactivation of liver-specific gene expression in an immortalized human hepatocyte cell line by introduction of the human HNF4alpha2 gene

Int J Mol Med. 2001 Nov;8(5):481-7. doi: 10.3892/ijmm.8.5.481.

Abstract

An immortalized human hepatocyte cell line (OUMS-29) was established from fetal liver by transfection with the SV-40 large T antigen gene that has certain liver-specific functions such as albumin production and enzyme activities of CYP1A1, 1A2, and 2E1. To make OUMS-29 cells express other liver-specific functions, the human hepatocyte nuclear factor 4alpha2 (HNF4alpha2) gene was introduced into the cells, because this gene was found to be markedly down-regulated. The transduced HNF4alpha2 was overexpressed in the nuclei of the transfected cells, and its DNA-binding activity was also detected. The liver-specific genes such as apolipoprotein AI, CII, CIII, blood coagulation factor X, alpha1-antitrypsin, and HNF1alpha were up-regulated. Thus, this cell line is expected to be a useful tool for studying the differentiated human hepatocyte functions.

MeSH terms

  • Apolipoprotein A-I / genetics
  • Apolipoprotein C-II
  • Apolipoprotein C-III
  • Apolipoproteins C / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Blotting, Northern
  • Cell Line
  • Cell Line, Transformed
  • DNA-Binding Proteins*
  • Down-Regulation
  • Electrophoresis, Polyacrylamide Gel
  • Electrophoretic Mobility Shift Assay
  • Factor X / genetics
  • Female
  • Gene Expression Regulation
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Hepatocyte Nuclear Factor 4
  • Hepatocytes / metabolism*
  • Humans
  • Liver / cytology
  • Liver / metabolism*
  • Male
  • Nuclear Proteins*
  • Oligonucleotides / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Phosphoproteins / physiology*
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Transfection
  • Tumor Cells, Cultured
  • alpha 1-Antitrypsin / genetics

Substances

  • Apolipoprotein A-I
  • Apolipoprotein C-II
  • Apolipoprotein C-III
  • Apolipoproteins C
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • HNF1A protein, human
  • HNF1B protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 4
  • MLX protein, human
  • Nuclear Proteins
  • Oligonucleotides
  • Phosphoproteins
  • RNA, Messenger
  • Transcription Factors
  • alpha 1-Antitrypsin
  • apolipoprotein C-II (St Michael)
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta
  • Factor X