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 RIS Download
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