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- Title
Synergy between tumor suppressor APC and the beta-catenin-Tcf4 target Tcf1.
- Authors
Roose, J; Huls, G; van Beest, M; Moerer, P; van der Horn, K; Goldschmeding, R; Logtenberg, T; Clevers, H
- Abstract
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.
- Publication
Science (New York, N.Y.), 1999, Vol 285, Issue 5435, p1923
- ISSN
0036-8075
- Publication type
Journal Article
- DOI
10.1126/science.285.5435.1923