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) |