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

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 t...

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Veröffentlicht in:Oncogene 1999-04, Vol.18 (16), p.2567-2577
Hauptverfasser: DEJARDIN, E, DEREGOWSKI, V, CHAPELIER, M, JACOBS, N, GIELEN, J, MERVILLE, M.-P, BOURS, V
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container_end_page 2577
container_issue 16
container_start_page 2567
container_title Oncogene
container_volume 18
creator DEJARDIN, E
DEREGOWSKI, V
CHAPELIER, M
JACOBS, N
GIELEN, J
MERVILLE, M.-P
BOURS, V
description 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.
doi_str_mv 10.1038/sj.onc.1202599
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source Nature; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
subjects Adenocarcinoma
Antisense oligonucleotides
Biological and medical sciences
Cancer
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Cytoplasm
Fundamental and applied biological sciences. Psychology
Molecular and cellular biology
NF-κB protein
Oligonucleotides
Reporter gene
Tax protein
Transcription
Tumor cell lines
Tumor necrosis factor-α
title Regulation of NF-κB activity by IκB-related proteins in adenocarcinoma cells
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