c-Jun N-terminal kinase negatively regulates epidermal growth factor-induced cyclooxygenase-2 expression in oral squamous cell carcinoma cell lines.
Epidermal growth factor (EGF)-induced cyclooxygenase-2 (COX-2) expression in squamous cell carcinomas is mediated through the extracellular signal-regulated kinase 1/2 and p38 pathways. Examination of a basaloid and a conventional oral squamous cell carcinoma cell line revealed that inhibition of c-Jun N-terminal kinase (JNK) with SP600125 increased EGF-induced (but not basal) COX-2 transcription 1.5-1.9-fold in extracellular signal-regulated kinase 1/2 and p38 pathway-dependent manners. Although JNK may phosphorylate the cyclosporine A-sensitive transcription factor, nuclear factor of activated T cells c3, it was seemingly not involved because cyclosporine A did not reduce EGF-induced COX-2 expression. Thus, JNK negatively regulated EGF-induced extracellular signal-regulated kinase 1/2 and/or p38-mediated COX-2 transcription, presumably through activating an unidentified phosphatase.
Husvik
Camilla
C
Department of Oral Biology, University of Oslo, Oslo, Norway.
Bryne
Magne
M
Halstensen
Trond S
TS
D000873:Anthracenes / Q000494:pharmacology; D065095:Calcineurin Inhibitors; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000032:analysis* / Q000187:drug effects / Q000235:genetics; D016572:Cyclosporine / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000032:analysis* / Q000187:drug effects / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000235:genetics; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000235:genetics; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000235:genetics; D050778:NFATC Transcription Factors / Q000187:drug effects; D010766:Phosphorylation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000235:genetics
D000873:Anthracenes; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D050778:NFATC Transcription Factors; D011500:Protein Synthesis Inhibitors; D003609:Dactinomycin; C432165:pyrazolanthrone; D004815:Epidermal Growth Factor; D016572:Cyclosporine; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases