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Regulation of NF-κB activity by IκB-related proteins in adenocarcinoma cells

Oncogene volume 18, pages 2567–2577 (1999)Cite this article

Abstract

Constitutive NF-κB activity varies widely among cancer cell lines. In this report, we studied the expression and the role of different IκB inhibitors in adenocarcinoma cell lines. High constitutive NF-κB activity and low IκB-α expression was found in a number of these cell lines. Moreover, some of these cells showed a high p100 expression, responsible for the cytoplasmic sequestration of most of p65 complexes. Treatment of these cells with TNF-α or other NF-κB activating agents induced only weakly nuclear NF-κB activity without significant p100 processing and led to a very weak transcription of NF-κB-dependent reporter gene. Induction of NF-κB activity can be restored by expression of the Tax protein or by treatment with antisense p100 oligonucleotides. In MCF7 A/Z cells stably transfected with a p100 expression vector, p65 complexes were sequestered in the cytoplasm by p100. These cells showed a reduced nuclear NF-κB induction and NF-κB-dependent gene transcription following TNF-α stimulation. As a consequence of a competition between IκB-α and p100, cells expressing high levels of p100 respond poorly to NF-κB activating stimuli as TNF-α.

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Acknowledgements

We thank Dr U Siebenlist (NIH, Bethesda, MD, USA) for the p50 and p52 anti-peptide antibodies, Dr K Wood (Freeman Hospital, Newcastle, UK) for the IκB-α monoclonal antibody Mad 10B, Dr N Rice (NCI, Frederick, USA) for c-Rel antibody, Dr J Brady (NIH, Bethesda, MD, USA) for the Tax antibody, Dr B van der Burg (Hubrecht Laboratory, Utrecht, Netherlands) for the 3xNF-κB(pIC)-tk-LUC plasmid, Dr Ghosh (Yale University, CT, USA) for the IκB-β cDNA, Dr J Koh (MGH Cancer Center, Charlestown, MA, USA) for the pCMV-CD20 expression plasmid and Professor Mareel (University of Ghent, Belgium) for the MCF7 A/Z cells. M-PM and VB are Research Associates at the National Fund for Scientific Research (Belgium). ED and VD are supported by Télévie and FRIA fellowships, respectively. This work has been supported by grants from the National Fund for Scientific Research (Belgium), Télévie (Belgium) and the Centre Anti Cancéreux (University of Liège, Belgium).

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  1. Laboratory of Medical Oncology and Medical Chemistry, University of Liège, Belgium

    Emmanuel Dejardin, Valérie Deregowski, Muriel Chapelier, Jacques Gielen, Marie-Paule Merville & Vincent Bours

  2. Department of Pathology, University of Liège, Belgium

    Nathalie Jacobs

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Dejardin, E., Deregowski, V., Chapelier, M. et al. Regulation of NF-κB activity by IκB-related proteins in adenocarcinoma cells. Oncogene 18, 2567–2577 (1999). https://doi.org/10.1038/sj.onc.1202599

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