Abstract
beta-catenin plays an important role in development and homeostasis. Deregulated beta-catenin is involved in oncogenesis. In this study, we found that beta-catenin can physically complex with NF-kappa B, resulting in a reduction of NF-kappa B DNA binding, transactivation activity, and target gene expression. Repressed NF-kappa B activity is found in human colon cancer cells in which beta-catenin is activated. Importantly, activated beta-catenin was found to inhibit the expression of NF-kappa B target genes, including Fas and TRAF1. Furthermore, a strong inverse correlation was identified between the expression levels of beta-catenin and Fas in colon and breast tumor tissues, suggesting that beta-catenin regulates NF-kappa B and its targets in vivo. Thus, beta-catenin may play an important role in oncogenesis through the crossregulation of NF-kappa B.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Colonic Neoplasms / metabolism*
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Colonic Neoplasms / pathology
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Cytoskeletal Proteins / pharmacology*
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DNA Primers / chemistry
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Down-Regulation
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Electrophoretic Mobility Shift Assay
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Female
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Flow Cytometry
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Gene Expression Regulation
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Glutathione Transferase / metabolism
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Humans
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I-kappa B Proteins / metabolism
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Immunoblotting
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Immunoenzyme Techniques
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Luciferases / metabolism
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Osteosarcoma / metabolism
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Osteosarcoma / pathology
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Precipitin Tests
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Promoter Regions, Genetic / immunology
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Protein Biosynthesis
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Trans-Activators / pharmacology*
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Transcriptional Activation
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Transfection
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Tumor Cells, Cultured / metabolism
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Tumor Cells, Cultured / pathology
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Tumor Necrosis Factor-alpha / pharmacology
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beta Catenin
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beta-Galactosidase / metabolism
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fas Receptor / metabolism
Substances
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CTNNB1 protein, human
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Cytoskeletal Proteins
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DNA Primers
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I-kappa B Proteins
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NF-kappa B
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Trans-Activators
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Tumor Necrosis Factor-alpha
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beta Catenin
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fas Receptor
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Luciferases
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Glutathione Transferase
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beta-Galactosidase