Epidermal growth factor-induced cyclooxygenase-2 expression in oral squamous cell carcinoma cell lines is mediated through extracellular signal-regulated kinase 1/2 and p38 but is Src and nuclear factor-kappa B independent.
The intracellular signalling cascade(s) mediating epidermal growth factor (EGF)-induced cyclooxygenase-2 (COX-2) expression is poorly defined in oral carcinomas. Investigation of two different oral squamous cell carcinoma (OSCC) cell lines with high EGF-induced COX-2 expression revealed, however, that this expression was dependent on two mitogen-activated protein kinase (MAPK) pathways [extracellular signal-regulated kinase 1/2 (ERK1/2) and p38] because combined inhibition of these pathways was needed to abolish EGF-induced COX-2 expression. Surprisingly, inhibition of phosphoinositide-3 kinase (PI3K) increased EGF-induced COX-2 expression in the basaloid OSCC cell line (C12), suggesting a PI3K-controlled, inhibitory COX-2-regulating pathway. Neither the transcription factor nuclear factor-kappaB (NF-kappaB), nor Src, was involved in EGF-induced COX-2 expression. The results suggest that EGF-induced COX-2 expression is regulated by several pathways, and emphasizes that individual tumors use different strategies for intracellular signalling.
Husvik
Camilla
C
Laboratory for mucosal immunology (LMI), Department of Oral Biology, University of Oslo, Oslo, Norway.
Bryne
Magne
M
Halstensen
Trond S
TS
D000368:Aged; D002281:Carcinoma, Basosquamous / Q000201:enzymology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D018289:Carcinoma, Verrucous / Q000201:enzymology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000032:analysis*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000502:physiology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D009062:Mouth Neoplasms / Q000201:enzymology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D052246:Cyclooxygenase 2 Inhibitors; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; D004815:Epidermal Growth Factor; D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D019061:src-Family Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases