Publication Date:
1997-03-21
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Korinek, V -- Barker, N -- Morin, P J -- van Wichen, D -- de Weger, R -- Kinzler, K W -- Vogelstein, B -- Clevers, H -- CA57345/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1997 Mar 21;275(5307):1784-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, University Hospital, Post Office Box 85500, 3508 GA Utrecht, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9065401" target="_blank"〉PubMed〈/a〉
Keywords:
Adenomatous Polyposis Coli Protein
;
Amino Acid Sequence
;
Animals
;
Cell Line
;
Cell Transformation, Neoplastic
;
Cloning, Molecular
;
Colon/metabolism
;
Colonic Neoplasms/*genetics/metabolism
;
Cytoskeletal Proteins/genetics/*metabolism
;
Gene Expression Regulation, Neoplastic
;
*Genes, APC
;
Genes, Reporter
;
Humans
;
Intestinal Mucosa/metabolism
;
Mice
;
Molecular Sequence Data
;
Signal Transduction
;
TCF Transcription Factors
;
*Trans-Activators
;
Transcription Factor 7-Like 2 Protein
;
Transcription Factors/chemistry/genetics/*metabolism
;
*Transcriptional Activation
;
Transfection
;
Tumor Cells, Cultured
;
beta Catenin
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
