Article (Scientific journals)
NF-kappaB-dependent MnSOD expression protects adenocarcinoma cells from TNF-alpha-induced apoptosis.
Delhalle, Sylvie; Deregowski, Valerie; Benoit, Valerie et al.
2002In Oncogene, 21 (24), p. 3917-24
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Keywords :
Adenocarcinoma/enzymology; Antioxidants/pharmacology; Apoptosis; Blotting, Western; Cell Survival; DNA, Complementary/metabolism; Dose-Response Relationship, Drug; Humans; NF-kappa B/metabolism; Plasmids/metabolism; Proto-Oncogene Proteins c-bcl-2/metabolism; Superoxide Dismutase/metabolism; Time Factors; Transfection; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha/metabolism; bcl-X Protein
Abstract :
[en] NF-kappaB is known to exert a cytoprotective action against TNF-alpha-induced apoptosis. To study the role of NF-kappaB in various TNF-alpha-treated epithelial cell lines, we generated stable transfectants overexpressing a mutated unresponsive form of the IkappaBalpha inhibitor (MT cells). As NF-kappaB prevented TNF-alpha-induced apoptosis in various epithelial cancer cell lines, we searched for NF-kappaB target gene products responsible for this difference of sensitivity. We observed an increased Bcl-X(L) expression level in OVCAR-3 cells compared with OVCAR-3 cells expressing a mutated IkappaBalpha inhibitor (MT cells). Induction of the antioxidant enzyme MnSOD was detected only in TNF-alpha-treated OVCAR, MCF7A/Z and HCT116 cells but not in MT cells. Moreover, reactive oxygen species were involved in TNF-alpha-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-alpha stimulation, partially restored resistance to TNF-alpha-induced cell death, as observed by clonogenic assays. However, transfection of the Bcl-X(L) cDNA did not induce any protective effect. Therefore, MnSOD expression is induced by NF-kappaB in epithelial cancer cells in response to TNF-alpha, and is at least partially responsible for their resistance to TNF-alpha-induced apoptosis, presumably through the clearance of death-inducing ROS.
Disciplines :
Genetics & genetic processes
Author, co-author :
Delhalle, Sylvie
Deregowski, Valerie
Benoit, Valerie
Merville, Marie-Paule ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Bours, Vincent ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine
Language :
English
Title :
NF-kappaB-dependent MnSOD expression protects adenocarcinoma cells from TNF-alpha-induced apoptosis.
Publication date :
2002
Journal title :
Oncogene
ISSN :
0950-9232
eISSN :
1476-5594
Publisher :
Nature Publishing Group, United Kingdom
Volume :
21
Issue :
24
Pages :
3917-24
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 28 February 2018

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