epidermal-growth-factor and Carcinoma--Verrucous

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.

Topics: Aged; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Carcinoma, Verrucous; Cell Line, Tumor; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Epidermal Growth Factor; ErbB Receptors; Female; Gene Expression Regulation, Enzymologic; Humans; Male; Middle Aged; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mouth Neoplasms; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphoinositide-3 Kinase Inhibitors; Signal Transduction; src-Family Kinases; Tumor Cells, Cultured