PKC-dependent modulation of IkB alpha-NFkB pathway in low metastatic B16F1 murine melanoma cells and in highly metastatic BL6 cells.
Protein Kinase C (PKC) is a family of at least 11 closely related isoforms with different modality of activation, and intracellular and tissue distribution. The aim of the present work was to analyse the effect of treatment with 0.1 microM TPA as well as treatment with specific inhibitors of individual PKC isoenzymes (Gö6976 for c-PKC alpha and beta isoforms and BIM for c-PKCs and n-PKCs isoforms), on the NF-kB/IkB alpha pathway in the low and high metastatic B16F1 and BL6 murine melanoma cells. The DNA-binding activity of the transcription factors AP1, AP2, CREB and OTC was also considered. Different modality of activation for NF-kB and AP1 was demonstrated in the two cell lines with the possible specific involvement of c-PKCs isoforms. In fact, in the high metastatic BL6 cells the long-term treatment for 24 hours with TPA, with no c-PKC activation or the inhibition with Gö6976 as well as with BIM, induced an increased NF-kB and AP1 DNA-binding activity. In contrast, in the low metastatic B16F1 cells the short-term treatment with TPA, induced the activation of c-PKCs isoforms, and enhanced NF-kB and AP1 DNA-binding activity. No significant changes were demonstrated for AP2, CREB and OTC DNA-binding activity in both cell lines.
La Porta
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CA
Department of General Physiology and Biochemistry, University of Milan, Italy. Caterina.LaPorta@unimi.it
Comolli
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D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020672:I-kappa B Proteins; D007211:Indoles / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009362:Neoplasm Metastasis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002227:Carbazoles; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; D007211:Indoles; D007527:Isoenzymes; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D018808:Transcription Factor AP-1; D050656:Transcription Factor AP-2; D014157:Transcription Factors; C081021:Go 6976; D000072000:NF-KappaB Inhibitor alpha; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D013755:Tetradecanoylphorbol Acetate