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 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenomatous Polyposis Coli Protein
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Amino Acid Sequence
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Animals
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Cell Line
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Cell Transformation, Neoplastic
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Cloning, Molecular
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Colon / metabolism
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Colonic Neoplasms / genetics*
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Colonic Neoplasms / metabolism
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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Gene Expression Regulation, Neoplastic
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Genes, APC*
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Genes, Reporter
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Humans
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Intestinal Mucosa / metabolism
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Mice
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Molecular Sequence Data
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Signal Transduction
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TCF Transcription Factors
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Trans-Activators*
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Transcription Factor 7-Like 2 Protein
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptional Activation*
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Transfection
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Tumor Cells, Cultured
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beta Catenin
Substances
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Adenomatous Polyposis Coli Protein
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CTNNB1 protein, human
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CTNNB1 protein, mouse
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Cytoskeletal Proteins
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TCF Transcription Factors
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TCF7L2 protein, human
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Tcf7l2 protein, mouse
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Trans-Activators
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Transcription Factor 7-Like 2 Protein
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Transcription Factors
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beta Catenin