title: Transduction of retinoic acid and gamma-interferon signal for intercellular adhesion molecule-1 expression on human tumor cell lines: evidence for the late-acting involvement of protein kinase C inactivation.
abstract: Intercellular adhesion molecule 1 (ICAM-1) is a major adhesion receptor of the immune system. Its cell surface expression on a wide variety of cells including cancer cells regulated by various proinflammatory cytokines. Incubation of the human glioma cell line HS 683 and the neuroblastoma cell line SK-N-SH with 12-phorbol 13-myristic acid (PMA), retinoic acid, or gamma-interferon (IFN-gamma) strongly stimulates ICAM-1 expression. In the present study, we investigated the role of the protein kinase C (PKC)-mediated signal transduction pathway in this process. We found that IFN-gamma, but not retinoic acid, was able to induce activation and translocation of PKC after 60 min in a dose-dependent fashion, contrasting with the very rapid activation and translocation induced by PMA which occurred at 15 min. The PKC inhibitors 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine dihydrochloride and staurosporine, as well as depletion of PKC by a 24-h treatment with 100 nM PMA, decreased the PMA-mediated stimulation but not the retinoic acid- or the IFN-gamma-mediated stimulation of ICAM-1 expression. On the contrary, they rather stimulated ICAM-1 expression. Furthermore, this stimulation was additive with retinoic acid and IFN-gamma. A 24-h incubation in the presence of retinoic acid or IFN-gamma strongly inhibited activation and translocation of PKC by PMA. These results suggest that although PMA-induced ICAM-1 expression is PKC dependent on HS 683 and SK-N-SH cells, the stimulation of ICAM-1 expression by retinoic acid and by IFN-gamma may be due to PKC inactivation at longer time points (24 h), as mimicked by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride, staurosporine, or PKC depletion by high doses of PMA.
authors.affiliation: Molecular Endocrinology Laboratory, CHUL Research Center, Québec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Bouillon
authors.forename: M
authors.initials: M
authors.lastname: Audette
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000470:Alkaloids; D015815:Cell Adhesion Molecules; D007546:Isoquinolines; D010879:Piperazines; D018799:Intercellular Adhesion Molecule-1; D014212:Tretinoin; D007371:Interferon-gamma; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate