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

Oncogene. 1999 Apr 22;18(16):2567-77. doi: 10.1038/sj.onc.1202599.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • DNA-Binding Proteins / metabolism
  • I-kappa B Proteins*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism*
  • NF-kappa B p52 Subunit
  • Oligonucleotides, Antisense
  • Protein Binding
  • Transcription, Genetic
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology


  • DNA-Binding Proteins
  • I-kappa B Proteins
  • NF-kappa B
  • NF-kappa B p52 Subunit
  • Oligonucleotides, Antisense
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha