beta-catenin interacts with and inhibits NF-kappa B in human colon and breast cancer

Cancer Cell. 2002 Oct;2(4):323-34. doi: 10.1016/s1535-6108(02)00154-x.

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

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Cytoskeletal Proteins / pharmacology*
  • DNA Primers / chemistry
  • Down-Regulation
  • Electrophoretic Mobility Shift Assay
  • Female
  • Flow Cytometry
  • Gene Expression Regulation
  • Glutathione Transferase / metabolism
  • Humans
  • I-kappa B Proteins / metabolism
  • Immunoblotting
  • Immunoenzyme Techniques
  • Luciferases / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • Precipitin Tests
  • Promoter Regions, Genetic / immunology
  • Protein Biosynthesis
  • Trans-Activators / pharmacology*
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / pathology
  • Tumor Necrosis Factor-alpha / pharmacology
  • beta Catenin
  • beta-Galactosidase / metabolism
  • fas Receptor / metabolism

Substances

  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA Primers
  • I-kappa B Proteins
  • NF-kappa B
  • Trans-Activators
  • Tumor Necrosis Factor-alpha
  • beta Catenin
  • fas Receptor
  • Luciferases
  • Glutathione Transferase
  • beta-Galactosidase