Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma.
Journal:
Science 1997 MarAuthors:
Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B, Clevers H
Abstract
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
...[more]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.[less]
Mesh Headings:
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