Regulation of NF-kappaB activity by I kappaB-related proteins in adenocarcinoma cells.
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.
Dejardin
E
E
Laboratory of Medical Oncology and Medical Chemistry, University of Liège, Belgium.
Deregowski
V
V
Chapelier
M
M
Jacobs
N
N
Gielen
J
J
Merville
M P
MP
Bours
V
V
D000230:Adenocarcinoma / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D052003:NF-kappa B p52 Subunit; D016376:Oligonucleotides, Antisense; D011485:Protein Binding; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D016376:Oligonucleotides, Antisense; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha