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Regulation of Nf-Kappab Activity by I Kappab-Related Proteins in Adenocarcinoma Cells
Dejardin, Emmanuel; Deregowski, Valérie; Chapelier, Muriel et al.
1999In Oncogene, 18 (16), p. 2567-77
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Abstract :
[en] Constitutive NF-kappaB activity varies widely among cancer cell lines. In this report, we studied the expression and the role of different I kappaB inhibitors in adenocarcinoma cell lines. High constitutive NF-kappaB activity and low I kappaB-alpha 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-alpha or other NF-kappaB activating agents induced only weakly nuclear NF-kappaB activity without significant p100 processing and led to a very weak transcription of NF-kappaB-dependent reporter gene. Induction of NF-kappaB 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-kappaB induction and NF-kappaB-dependent gene transcription following TNF-alpha stimulation. As a consequence of a competition between I kappaB-alpha and p100, cells expressing high levels of p100 respond poorly to NF-kappaB activating stimuli as TNF-alpha.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Dejardin, Emmanuel ;  Université de Liège - ULiège > Virologie - Immunologie
Deregowski, Valérie
Chapelier, Muriel
Jacobs, Nathalie  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Gielen, Jacques
Merville, Marie-Paule ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Bours, Vincent ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique générale et humaine
Language :
English
Title :
Regulation of Nf-Kappab Activity by I Kappab-Related Proteins in Adenocarcinoma Cells
Publication date :
22 April 1999
Journal title :
Oncogene
ISSN :
0950-9232
eISSN :
1476-5594
Publisher :
Nature Publishing Group, United Kingdom
Volume :
18
Issue :
16
Pages :
2567-77
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 11 August 2009

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