β-catenin interacts with and inhibits NF-κB in human colon and breast cancer

Jiong Deng, Stephanie A. Miller, Hong Ying Wang, Weiya Xia, Yong Wen, Binhua P. Zhou, Yan Li, Shiaw Yih Lin, Mien Chie Hung

Research output: Contribution to journalArticlepeer-review

305 Scopus citations

Abstract

β-catenin plays an important role in development and homeostasis. Deregulated β-catenin is involved in oncogenesis. In this study, we found that β-catenin can physically complex with NF-κB, resulting in a reduction of NF-κB DNA binding, transactivation activity, and target gene expression. Repressed NF-κB activity is found in human colon cancer cells in which β-catenin is activated. Importantly, activated β-catenin was found to inhibit the expression of NF-κB target genes, including Fas and TRAF1. Furthermore, a strong inverse correlation was identified between the expression levels of β-catenin and Fas in colon and breast tumor tissues, suggesting that β-catenin regulates NF-κB and its targets in vivo. Thus, β-catenin may play an important role in oncogenesis through the crossregulation of NF-κB.

Original languageEnglish
Pages (from-to)323-334
Number of pages12
JournalCancer Cell
Volume2
Issue number4
DOIs
StatePublished - Oct 2002

Bibliographical note

Funding Information:
This work was supported by NIH grants CA58880 and Ovarian SPORE grant P50 CA83639 (to M.-C. Hung), by a predoctoral fellowship from the US Army Breast Cancer Research Training Grant Program, Grant No. DAMD17-99-1-9264 (to Y. Wen), and Grant No. DAMD 17-02-1-0454 (to Y. Li). We would like to thank Dr. S.W. Byers for the wild type β-catenin and β-cateninS37A plasmids, Dr. H. Clevers for the dominant negative TCF4 (pcDNA3-ΔNTCF4), TOP, and FOP plasmids, and Dr. L.K. Su for the APC expression plasmid. We would also like to thank Dr. A.G. de Herreros for the GST-β-catenin, Dr. P.J. Chiao for the pBS-p65 and pBS-p105 and MEF rela −/− cells, and Dr. J. Schmid for the GFP-p65 plasmid.

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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