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Regulation of NF-kappaB activity by I kappaB-related proteins in adenocarcinoma cells.

Abstract：

: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.

journal_name

Oncogene

journal_title

Oncogene

authors

Dejardin E,Deregowski V,Chapelier M,Jacobs N,Gielen J,Merville MP,Bours V

doi

10.1038/sj.onc.1202599

subject

Has Abstract

pub_date

1999-04-22 00:00:00

pages

2567-77

issue

16

eissn

0950-9232

issn

1476-5594

journal_volume

18

pub_type

杂志文章

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