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Identification of membrane-type matrix metalloproteinase-1 as a target of the β-catenin/Tcf4 complex in human colorectal cancers
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Identification of membrane-type matrix metalloproteinase-1 as a target of the β-catenin/Tcf4 complex in human colorectal cancers
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Identification of membrane-type matrix metalloproteinase-1 as a target of the β-catenin/Tcf4 complex in human colorectal cancers
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Journal Article
Identification of membrane-type matrix metalloproteinase-1 as a target of the β-catenin/Tcf4 complex in human colorectal cancers
2002
Overview
Genetic alterations of APC and CTNNB1 (beta-catenin) have been identified in a number of human cancers including tumors arising in the colon and liver. Mutations in these genes lead to abnormal accumulation of beta-catenin and constitutive activation of target genes in the Wnt signaling pathway. To clarify the precise role of accumulated beta-catenin in colorectal carcinogenesis, we searched for genes involved in the beta-catenin/Tcf signaling pathway by cDNA microarray. MT1-MMP (membrane-type matrix metalloproteinase) was among 84 genes that were down-regulated after beta-catenin had been depleted by transduction of wild-type APC in SW480 cells. Expression of MT1-MMP was elevated in 22 of 24 colon carcinomas we examined. Reporter assays and an electromobility-shift assay revealed a DNA fragment between -1169 bp and -1163 bp in the 5' flanking region of this gene to be a target of the beta-catenin/Tcf4 complex. Our results indicate that MT1-MMP is a direct down-stream target in the Wnt signaling pathway, and that one of the ways accumulated beta-catenin contributes to colorectal carcinogenesis is by transactivating this gene.
Publisher
Nature Publishing,Nature Publishing Group
Subject
/ Biological and medical sciences
/ Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
/ Colon
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - metabolism
/ Cytoskeletal Proteins - metabolism
/ Fundamental and applied biological sciences. Psychology
/ Genes
/ Humans
/ Matrix Metalloproteinases, Membrane-Associated
/ Metalloendopeptidases - genetics
/ Metalloendopeptidases - metabolism
/ Molecular and cellular biology
/ Trans-Activators - metabolism
/ Transcription Factor 7-Like 2 Protein
/ Transcription Factors - metabolism
/ Tumors
