beta-catenin interacts with and inhibits NF-kappa B in human colon and breast cancer.
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.
Deng
Jiong
J
Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.
Miller
Stephanie A
SA
Wang
Hong-Ying
HY
Xia
Weiya
W
Wen
Yong
Y
Zhou
Binhua P
BP
Li
Yan
Y
Lin
Shiaw-Yih
SY
Hung
Mien-Chie
MC
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000494:pharmacology*; D017931:DNA Primers / Q000737:chemistry; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000276:immunology; D014176:Protein Biosynthesis; D015534:Trans-Activators / Q000494:pharmacology*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051176:beta Catenin; D001616:beta-Galactosidase / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D020672:I-kappa B Proteins; D016328:NF-kappa B; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin; D019014:fas Receptor; D008156:Luciferases; D005982:Glutathione Transferase; D001616:beta-Galactosidase