Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aged
-
Carcinoma, Basosquamous / enzymology
-
Carcinoma, Squamous Cell / enzymology*
-
Carcinoma, Verrucous / enzymology
-
Cell Line, Tumor
-
Cyclooxygenase 2 / analysis*
-
Cyclooxygenase 2 Inhibitors / pharmacology
-
Epidermal Growth Factor / physiology*
-
ErbB Receptors / antagonists & inhibitors
-
Female
-
Gene Expression Regulation, Enzymologic
-
Humans
-
Male
-
Middle Aged
-
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
-
Mitogen-Activated Protein Kinase 1 / physiology*
-
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
-
Mitogen-Activated Protein Kinase 3 / physiology*
-
Mouth Neoplasms / enzymology*
-
NF-kappa B / antagonists & inhibitors
-
NF-kappa B / physiology*
-
Phosphoinositide-3 Kinase Inhibitors
-
Signal Transduction / physiology
-
Tumor Cells, Cultured
-
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
-
p38 Mitogen-Activated Protein Kinases / physiology*
-
src-Family Kinases / antagonists & inhibitors
-
src-Family Kinases / physiology*
Substances
-
Cyclooxygenase 2 Inhibitors
-
NF-kappa B
-
Phosphoinositide-3 Kinase Inhibitors
-
Epidermal Growth Factor
-
Cyclooxygenase 2
-
ErbB Receptors
-
src-Family Kinases
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3
-
p38 Mitogen-Activated Protein Kinases