Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC${-/-}$ Colon Carcinoma

• Published in: Science (American Association for the Advancement of Science) Vol. 275; no. 5307; pp. 1784 - 1787
• Main Authors: Korinek, Vladimir, Barker, Nick, Morin, Patrice J., van Wichen, Dick, de Weger, Roel, Kinzler, Kenneth W., Vogelstein, Bert, Clevers, Hans
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 21.03.1997; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: 3T3 cells; Adenomatous Polyposis Coli Protein; Amino Acid Sequence; Animals; B lymphocytes; beta Catenin; Biological and medical sciences; Cancer; Carcinoma; Cell Line; Cell lines; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Neoplastic; Cloning, Molecular; Colon - metabolism; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colorectal cancer; COS cells; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Epithelial cells; Familial polyposis; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Neoplastic; Genes; Genes, APC; Genes, Reporter; Genetic aspects; Genetic transcription; Humans; Intestinal Mucosa - metabolism; Medical research; Mice; Molecular and cellular biology; Molecular Sequence Data; Plasmids; Polyposis, Familial; Proteins; Reporter genes; Signal Transduction; T lymphocytes; TCF Transcription Factors; Trans-Activators; Transcription (Genetics); Transcription Factor 7-Like 2 Protein; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional Activation; Transfection; Tumor Cells, Cultured; Human; Nucleotide sequence; Homology; Molecular interaction; Gene expression; Cell transformation; Signal transduction; Complementary DNA; Gene; Digestive diseases; Intestinal disease; Tumor; Molecular complex; Colon; Mutation; Catenin; Tumor suppressor gene
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.275.5307.1784

The adenomatous polyposis coli (APC) tumor suppressor protein binds to β-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 β-catenin. Nuclei of APC$^{-/-}$ colon carcinoma cells were found to contain a stable β-catenin-hTcf-4 complex that was constitutively active, as measured by transcription of a Tcf reporter gene. Reintroduction of APC removed β-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.