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NF-κB-dependent MnSOD expression protects adenocarcinoma cells from TNF-α-induced apoptosis

Oncogene volume 21, pages 3917–3924 (2002)Cite this article

Abstract

NF-κB is known to exert a cytoprotective action against TNF-α-induced apoptosis. To study the role of NF-κB in various TNF-α-treated epithelial cell lines, we generated stable transfectants overexpressing a mutated unresponsive form of the IκBα inhibitor (MT cells). As NF-κB prevented TNF-α-induced apoptosis in various epithelial cancer cell lines, we searched for NF-κB target gene products responsible for this difference of sensitivity. We observed an increased Bcl-XL expression level in OVCAR-3 cells compared with OVCAR-3 cells expressing a mutated IκBα inhibitor (MT cells). Induction of the antioxidant enzyme MnSOD was detected only in TNF-α-treated OVCAR, MCF7A/Z and HCT116 cells but not in MT cells. Moreover, reactive oxygen species were involved in TNF-α-induced apoptosis, as various antioxidants partially protected these cells from apoptosis. At last, transfection of the MnSOD cDNA in MT cells, which do not express this protein after TNF-α stimulation, partially restored resistance to TNF-α-induced cell death, as observed by clonogenic assays. However, transfection of the Bcl-XL cDNA did not induce any protective effect. Therefore, MnSOD expression is induced by NF-κB in epithelial cancer cells in response to TNF-α, and is at least partially responsible for their resistance to TNF-α-induced apoptosis, presumably through the clearance of death-inducing ROS.

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Acknowledgements

The authors are grateful to Dr Chouaib (IGR, Villejuif, France) for the gift of the MnSOD cDNA, and to Dr Bertrand (Université de Montréal, Canada) for the gift of the Bcl-XL plasmid. M-P Merville is a Research Associate and V Benoit is a Research Assistant of the National Fund for Scientific Research. (‘FNRS’, Belgium). S Delhalle is supported by a Télévie grant (Belgium), and V Deregowski is supported by the Centre Anti Cancéreux (University of Liège, Belgium). This work was supported by grants from the National Fund for Scientific Research (‘FNRS’), and the ‘Centre Anti-Cancéreux’ (Liège, Belgium).

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  1. Laboratory of Medical Chemistry and Human Genetics, Center for Cellular and Molecular Therapy, University of Liège, Belgium

    Sylvie Delhalle, Valérie Deregowski, Valérie Benoit, Marie-Paule Merville & Vincent Bours

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  1. Sylvie Delhalle
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  2. Valérie Deregowski
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  3. Valérie Benoit
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  4. Marie-Paule Merville
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  5. Vincent Bours
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Correspondence to Vincent Bours.

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Delhalle, S., Deregowski, V., Benoit, V. et al. NF-κB-dependent MnSOD expression protects adenocarcinoma cells from TNF-α-induced apoptosis. Oncogene 21, 3917–3924 (2002). https://doi.org/10.1038/sj.onc.1205489

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