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.
MeSH terms
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Adenoma / genetics
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Adenoma / metabolism
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Adenoma / pathology
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Adenomatous Polyposis Coli Protein
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Animals
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Cytoskeletal Proteins / metabolism*
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Female
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Gene Expression Regulation, Neoplastic
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Genes, Tumor Suppressor
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Hepatocyte Nuclear Factor 1-alpha
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Humans
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Intestinal Neoplasms / genetics
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Intestinal Neoplasms / metabolism
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Intestinal Neoplasms / pathology
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Lymphoid Enhancer-Binding Factor 1
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Male
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Mammary Neoplasms, Experimental / genetics
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Mammary Neoplasms, Experimental / metabolism
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Mammary Neoplasms, Experimental / pathology
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Mice
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Neoplasm Proteins / metabolism
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Promoter Regions, Genetic
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T Cell Transcription Factor 1
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TCF Transcription Factors
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Trans-Activators*
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Transcription Factor 7-Like 2 Protein
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Transcription Factors / genetics*
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Transcription Factors / metabolism*
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Transfection
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Tumor Cells, Cultured
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beta Catenin
Substances
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Adenomatous Polyposis Coli Protein
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CTNNB1 protein, human
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CTNNB1 protein, mouse
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Hepatocyte Nuclear Factor 1-alpha
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Hnf1a protein, mouse
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Lymphoid Enhancer-Binding Factor 1
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Neoplasm Proteins
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T Cell Transcription Factor 1
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TCF Transcription Factors
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TCF7 protein, human
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TCF7L2 protein, human
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Tcf7l2 protein, mouse
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Trans-Activators
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Transcription Factor 7-Like 2 Protein
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Transcription Factors
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beta Catenin