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

Constitutive NF-kappa B activity varies widely among cancer cell lines. In this report, we studied the expression and the role of different I kappa B inhibitors in adenocarcinoma cell lines. High constitutive NF-kappa B activ ity and low I kappa B-alpha expression was found in a number of these cell lines. Moreover, some of these cells showed a high p100 expression, respons ible for the cytoplasmic sequestration of most of p65 complexes. Treatment of these cells with TNF-alpha or other NF-kappa B activating agents induced only weakly nuclear NF-kappa B activity without significant p100 processin g and led to a very weak transcription of NF-kappa B-dependent reporter gen e. Induction of NF-kappa B activity can be restored by expression of the Ta x 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-KB induction and NF-kappa B-dependent gene transcription following TNF- x stimulation. As a consequence of a competition between I kappa B-alpha an d p100, cells expressing high levels of p100 respond poorly to NF-kappa B a ctivating stimuli as TNF-alpha.