Crossregulation of NF-κB by the APC/GSK-3β/β-catenin pathway
Article first published online: 22 FEB 2004
Copyright © 2004 Wiley-Liss, Inc.
Volume 39, Issue 3, pages 139–146, March 2004
How to Cite
Deng, J., Xia, W., Miller, S. A., Wen, Y., Wang, H.-Y. and Hung, M.-C. (2004), Crossregulation of NF-κB by the APC/GSK-3β/β-catenin pathway. Mol. Carcinog., 39: 139–146. doi: 10.1002/mc.10169
- Issue published online: 22 FEB 2004
- Article first published online: 22 FEB 2004
- Manuscript Accepted: 5 NOV 2003
- Manuscript Revised: 27 OCT 2003
- Manuscript Received: 28 MAY 2003
- breast cancer
Glycogen synthase kinase-3β (GSK-3β) and adenomatous polyposis coli (APC) play an important role in the regulation of β-catenin. Inhibition of or defects in their functions can lead to activation of β-catenin. β-catenin has been recently found to interact with and inhibit nuclear factor kappa B (NF-κB). However, the regulatory roles of GSK-3β/APC on the NF-κB signaling pathway are unknown because of their diverse effects. In this study, we investigated whether GSK-3β/APC might regulate NF-κB activity through β-catenin. We found that inhibition of GSK-3β suppressed NF-κB activity, whereas reexpression of APC restored NF-κB activity in APC mutated cells. The regulatory effects were through β-catenin because depletion of β-catenin with small interfering RNA (siRNA) in the same systems reversed the effects. The regulatory relationship was further supported by the analysis of primary breast tumor tissues in vivo in which NF-κB target TRAF1 was inversely correlated with activated β-catenin. Thus, APC/GSK-3β, through β-catenin, may crossregulate NF-κB signaling pathway. © 2004 Wiley-Liss, Inc.