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

Abstract

Numerous investigations show that cytokines have a significant role in the regulation of cell growth. There is also increasing evidence for the role of transcription factors in cytokine-mediated growth-regulation of cancer cells. Our previous data demonstrate that several cytokines are able to inhibit DNA synthesis of vulvar carcinoma cells. The aim of this study was to investigate the effect of growth-inhibitory cytokines on the binding activity of transcription factor AP-1 and NF-κB in two vulvar carcinoma cell lines UM-SCV-6 and UM-SCV-1A in vitro. The effects of interferon γ (IFN-γ), interleukins 10 (IL-10) and 13 (IL-13), transforming growth factor β 1 (TGF-β 1) and tumor necrosis factor α (TNF-α) on the DNA binding proteins were studied by electrophoretic mobility shift assay (EMSA). Our results showed that NF-κB and AP-1 were constitutively activated in both cell lines. The binding activity of NF-κB was found to be stimulated by TNF-α in both vulvar carcinoma cell lines while no effect on AP-1 was found by any of the cytokines. The binding activity of NF-κB was decreased by IL-10 and IL-13 in UM-SCV-1A cells suggesting that the pathway by which TNF-α activates NF-κB differs from that activated by interleukins.