RRC ID 42068
著者 Sasaki E, Tominaga K, Watanabe T, Fujiwara Y, Oshitani N, Matsumoto T, Higuchi K, Tarnawski AS, Arakawa T.
タイトル COX-2 is essential for EGF induction of cell proliferation in gastric RGM1 cells.
ジャーナル Dig Dis Sci
Abstract Growth factors upregulate cyclooxygenase-2 (COX-2) expression and extracellular signal-regulated kinase (ERK) activity, yet little is known regarding the interaction between COX-2 and ERK in terms of mitogenic signal transduction pathways in gastric epithelial cells. Therefore, we examined the role of COX-2 in EGF-induced proliferation of gastric epithelial RGM1 cells. EGF treatment significantly induced ERK activity (peaked at 30 min) and significantly increased COX-2 protein (peaked at 6 hr), production of prostaglandin E2 (PGE2), and cell proliferation. MEK inhibitor (PD98059) decreased ERK activity and cell proliferation induced by EGF. The selective COX-2 inhibitor (NS-398) significantly reduced EGF-induced cell proliferation. Exogenous PGE2 partly reversed the NS-398-induced inhibitory action on cell proliferation, clearly indicating the importance of PGE2 in mitogenic pathway. The induction of COX-2 protein by EGF was completely blocked by preincubation with MEK inhibitor. These results suggest that the ERK-COX-2 pathway is critical for EGF-induced proliferation of gastric epithelial cells.
巻・号 48(12)
ページ 2257-62
公開日 2003-12-1
DOI 10.1023/b:ddas.0000007860.87503.09
PMID 14714610
MeSH Animals Blotting, Western Cell Division / drug effects Cells, Cultured / drug effects Cells, Cultured / metabolism Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors / pharmacology Dinoprostone / metabolism* Epidermal Growth Factor / pharmacology* Flavonoids / pharmacology Gastric Mucosa / metabolism* Isoenzymes / antagonists & inhibitors Isoenzymes / drug effects Isoenzymes / metabolism* Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors Mitogen-Activated Protein Kinases / drug effects Mitogen-Activated Protein Kinases / metabolism* Nitrobenzenes / pharmacology Prostaglandin-Endoperoxide Synthases / drug effects Prostaglandin-Endoperoxide Synthases / metabolism* Rats Signal Transduction Stomach / cytology* Sulfonamides / pharmacology
IF 2.751
引用数 19
WOS 分野 GASTROENTEROLOGY & HEPATOLOGY
リソース情報
ヒト・動物細胞 RGM1(RCB0876)