Abstract
Most colorectal cancers have loss of function mutations in the adenomatosis polyposis coli (APC) tumor suppressor gene. This leads to accumulation of beta-catenin, which together with the DNA binding protein TCF-4 functions as a transcriptional activator. Recently defined target genes are c-myc and cyclin D1, linking the APC gene defect to the capacity for autonomous proliferation of colon tumors. Here we report the identification of the matrix metalloproteinase MMP-7 as another target gene of beta-catenin/TCF-4. MMP-7 is overexpressed in 80% of human colorectal cancers and known to be an important factor for early tumor growth, with a potential function also for later progression steps, like invasion and metastasis. Our results explain the high percentage of MMP-7 overexpression in colon tumors. Moreover they indicate that defects in the APC tumor suppressor gene may also have an influence on later steps of colon tumor progression.
MeSH terms
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Biomarkers, Tumor / metabolism
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Cell Nucleus / metabolism
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Colorectal Neoplasms / enzymology*
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Colorectal Neoplasms / genetics
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Colorectal Neoplasms / metabolism
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Cytoskeletal Proteins / metabolism
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Cytoskeletal Proteins / physiology*
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Gene Expression Regulation, Neoplastic
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Genes, APC
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Genes, Dominant
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Glutathione Transferase / genetics
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Glutathione Transferase / metabolism
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HT29 Cells
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HeLa Cells
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Humans
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Immunohistochemistry
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Matrix Metalloproteinase 7 / biosynthesis*
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Matrix Metalloproteinase 7 / genetics
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Promoter Regions, Genetic / genetics
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Recombinant Fusion Proteins / metabolism
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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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beta Catenin
Substances
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Biomarkers, Tumor
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CTNNB1 protein, human
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Cytoskeletal Proteins
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Recombinant Fusion Proteins
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TCF Transcription Factors
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TCF7L2 protein, human
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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
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Glutathione Transferase
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Matrix Metalloproteinase 7