Synergy between tumor suppressor APC and the beta-catenin-Tcf4 target Tcf1

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 the se adenomas. Tcf1 may act as a feedback repressor of beta-catenin-Tcf4 targ et genes and thus may cooperate with APC to suppress malignant transformati on of epithelial cells.