Activation of transcription factor NF-kappa B by growth inhibitory cytokines in vulvar carcinoma cells

Numerous investigations show that cytokines have a significant role in the regulation of cell growth. There is also increasing evidence for the role o f transcription factors in cytokine-mediated growth-regulation of cancer ce lls. Our previous data demonstrate that several cytokines are able to inhib it DNA synthesis of vulvar carcinoma cells. The aim of this study was to in vestigate the effect of growth-inhibitory cytokines on the binding activity of transcription factor AP-1 and NF-kappa B in two vulvar carcinoma cell l ines UM-SCV-6 and UM-SCV-1A in vitro. The effects of interferon gamma (IFN- gamma), interleukins 10 (IL-10) and 13 (IL-13), transforming growth factor beta(1) (TGF-beta(1)) and tumor necrosis factor alpha (TNF-alpha) on the D NA binding proteins were studied by electrophoretic mobility shift assay (E MSA). Our results showed that NF-kappa B and AP-1 were constitutively activ ated in both cell lines. The binding activity of NF-kappa B was found to be stimulated by TNF-alpha in both vulvar carcinoma cell lines while no effec t on AP-I was found by any of the cytokines. The binding activity of NF-kap pa B was decreased by IL-10 and IL-13 in UM-SCV-1A cells suggesting that th e pathway by which TNF-alpha activates NF-kappa B differs from that activat ed by interleukins. (C) 2000 Published by Elsevier Science B.V. All rights reserved.