Aberrant expression and function of TCF4 in the proliferation of hepatocellular carcinoma cell line BEL-7402

Cell Res. 2004 Feb;14(1):74-80. doi: 10.1038/sj.cr.7290205.

Abstract

Wnt signaling pathway is essential for development and tumorigenesis, however, this signaling pathway in the progress of hepatocellular carcinoma (HCC) remains unclear. In this paper, we studied the function of human T-cell transcription factor-4 (TCF4), a key factor of Wnt signaling pathway, on the proliferation of HCC cell line. We showed that the expression of TCF4 mRNA in HCC cell line BEL-7402 was higher than that in immortalized normal liver cell line L02. Blockage of Wnt pathway by Delta-NTCF4, a dominant negative TCF4, could suppress BEL-7402 cells growth and decrease the expression of cyclin D1 and c-myc, two of target genes of Wnt pathway. On the other hand, stimulating Wnt pathway by introducing a degradation-resistant -catenin S37A could increase BEL-7402 cells proliferation. But all the treatments had no effect on L02 cells. Our data indicated that TCF4 might be another key factor in Wnt pathway involved in HCC cells proliferation and TCF4 could be an effective therapeutic target for suppressing the growth of hepatocellular cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / physiopathology*
  • Cell Division / genetics
  • Cell Division / physiology
  • Cell Line
  • Cell Line, Tumor
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cytoplasm / chemistry
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / physiology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter / genetics
  • Genetic Vectors / genetics
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / physiopathology*
  • Lymphoid Enhancer-Binding Factor 1
  • Microscopy, Fluorescence
  • Mutation / genetics
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology
  • Spectrometry, Fluorescence
  • TCF Transcription Factors
  • Trans-Activators / analysis
  • Trans-Activators / genetics
  • Trans-Activators / physiology
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transfection
  • Wnt Proteins
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • MYC protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Trans-Activators
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • Wnt Proteins
  • beta Catenin
  • Cyclin D1