PMID- 9065401 OWN - NLM STAT- MEDLINE DCOM- 19970422 LR - 20240104 IS - 0036-8075 (Print) IS - 0036-8075 (Linking) VI - 275 IP - 5307 DP - 1997 Mar 21 TI - Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. PG - 1784-7 AB - 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. FAU - Korinek, V AU - Korinek V AD - Department of Immunology, University Hospital, Post Office Box 85500, 3508 GA Utrecht, Netherlands. FAU - Barker, N AU - Barker N FAU - Morin, P J AU - Morin PJ FAU - van Wichen, D AU - van Wichen D FAU - de Weger, R AU - de Weger R FAU - Kinzler, K W AU - Kinzler KW FAU - Vogelstein, B AU - Vogelstein B FAU - Clevers, H AU - Clevers H LA - eng SI - GENBANK/Y11306 GR - CA57345/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (Adenomatous Polyposis Coli Protein) RN - 0 (CTNNB1 protein, human) RN - 0 (CTNNB1 protein, mouse) RN - 0 (Cytoskeletal Proteins) RN - 0 (TCF Transcription Factors) RN - 0 (TCF7L2 protein, human) RN - 0 (Tcf7l2 protein, mouse) RN - 0 (Trans-Activators) RN - 0 (Transcription Factor 7-Like 2 Protein) RN - 0 (Transcription Factors) RN - 0 (beta Catenin) SB - IM CIN - Science. 1997 Mar 21;275(5307):1752-3. PMID: 9122680 MH - Adenomatous Polyposis Coli Protein MH - Amino Acid Sequence MH - Animals MH - Cell Line MH - Cell Transformation, Neoplastic MH - Cloning, Molecular MH - Colon/metabolism MH - Colonic Neoplasms/*genetics/metabolism MH - Cytoskeletal Proteins/genetics/*metabolism MH - Gene Expression Regulation, Neoplastic MH - *Genes, APC MH - Genes, Reporter MH - Humans MH - Intestinal Mucosa/metabolism MH - Mice MH - Molecular Sequence Data MH - Signal Transduction MH - TCF Transcription Factors MH - *Trans-Activators MH - Transcription Factor 7-Like 2 Protein MH - Transcription Factors/chemistry/genetics/*metabolism MH - *Transcriptional Activation MH - Transfection MH - Tumor Cells, Cultured MH - beta Catenin EDAT- 1997/03/21 00:00 MHDA- 1997/03/21 00:01 CRDT- 1997/03/21 00:00 PHST- 1997/03/21 00:00 [pubmed] PHST- 1997/03/21 00:01 [medline] PHST- 1997/03/21 00:00 [entrez] AID - 10.1126/science.275.5307.1784 [doi] PST - ppublish SO - Science. 1997 Mar 21;275(5307):1784-7. doi: 10.1126/science.275.5307.1784.