Synergy Between Tumor Suppressor APC and the β-Catenin-Tcf4 Target Tcf1

Abstract
Mutations in APC or β-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 β-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 β-catenin–Tcf4 target genes and thus may cooperate with APC to suppress malignant transformation of epithelial cells.