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Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma.

The adenomatous polyposis coli (APC) tumor suppressor protein binds to beta-catenin, a protein recently shown to interact with Tcf and Lef transcription factors. The gene encoding hTcf-4, a Tcf family member that is expressed in colonic epithelium, was cloned and characterized. hTcf-4 transactivates transcription only when associated with beta-catenin. Nuclei of APC-/- colon carcinoma cells were found to contain a stable beta-catenin-hTcf-4 complex that was constitutively active, as measured by transcription of a Tcf reporter gene. Reintroduction of APC removed beta-catenin from hTcf-4 and abrogated the transcriptional transactivation. Constitutive transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium.

Pubmed ID: 9065401


  • Korinek V
  • Barker N
  • Morin PJ
  • van Wichen D
  • de Weger R
  • Kinzler KW
  • Vogelstein B
  • Clevers H


Science (New York, N.Y.)

Publication Data

March 21, 1997

Associated Grants

  • Agency: NCI NIH HHS, Id: CA57345

Mesh Terms

  • Adenomatous Polyposis Coli Protein
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cell Transformation, Neoplastic
  • Cloning, Molecular
  • Colon
  • Colonic Neoplasms
  • Cytoskeletal Proteins
  • Gene Expression Regulation, Neoplastic
  • Genes, APC
  • Genes, Reporter
  • Humans
  • Intestinal Mucosa
  • Mice
  • Molecular Sequence Data
  • Signal Transduction
  • TCF Transcription Factors
  • Trans-Activators
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured
  • beta Catenin