Publication Date:
1999-09-18
Description:
Mutations in APC or beta-catenin inappropriately activate the transcription factor Tcf4, thereby transforming intestinal epithelial cells. Here it is shown that one of the target genes of Tcf4 in epithelial cells is Tcf1. The most abundant Tcf1 isoforms lack a beta-catenin interaction domain. Tcf1(-/-) mice develop adenomas in the gut and mammary glands. Introduction of a mutant APC allele into these mice substantially increases the number of these adenomas. Tcf1 may act as a feedback repressor of beta-catenin-Tcf4 target genes and thus may cooperate with APC to suppress malignant transformation of epithelial cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roose, J -- Huls, G -- van Beest, M -- Moerer, P -- van der Horn, K -- Goldschmeding, R -- Logtenberg, T -- Clevers, H -- New York, N.Y. -- Science. 1999 Sep 17;285(5435):1923-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Center for Biomedical Genetics, Department of Pathology, University Medical Center Utrecht, 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/10489374" target="_blank"〉PubMed〈/a〉
Keywords:
Adenoma/genetics/metabolism/pathology
;
Adenomatous Polyposis Coli Protein
;
Animals
;
Cytoskeletal Proteins/*metabolism
;
DNA-Binding Proteins/*genetics/metabolism
;
Female
;
Gene Expression Regulation, Neoplastic
;
Genes, Tumor Suppressor
;
Hepatocyte Nuclear Factor 1-alpha
;
Humans
;
Intestinal Neoplasms/genetics/metabolism/pathology
;
Lymphoid Enhancer-Binding Factor 1
;
Male
;
Mammary Neoplasms, Experimental/genetics/metabolism/pathology
;
Mice
;
Neoplasm Proteins/metabolism
;
Promoter Regions, Genetic
;
T Cell Transcription Factor 1
;
TCF Transcription Factors
;
*Trans-Activators
;
Transcription Factor 7-Like 2 Protein
;
Transcription Factors/*genetics/*metabolism
;
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
