Activation of transcription factor NF-kappaB 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 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-kappaB in two vulvar carcinoma cell lines 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 DNA binding proteins were studied by electrophoretic mobility shift assay (EMSA). Our results showed that NF-kappaB and AP-1 were constitutively activated in both cell lines. The binding activity of NF-kappaB was found to be stimulated by TNF-alpha in both vulvar carcinoma cell lines while no effect on AP-1 was found by any of the cytokines. The binding activity of NF-kappaB was decreased by IL-10 and IL-13 in UM-SCV-1A cells suggesting that the pathway by which TNF-alpha activates NF-kappaB differs from that activated by interleukins.
Seppänen
M
M
Department of Obstetrics and Gynecology and Institute of Medical Technology (IMT), University of Tampere, Medical School, Lenkkeilijänkatu 6, FIN-33520, Tampere, Finland.
Vihko
K K
KK
D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D004586:Electrophoresis; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014846:Vulvar Neoplasms / Q000378:metabolism*
D016207:Cytokines; D018793:Interleukin-13; D016328:NF-kappa B; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma