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COX-2 Is Essential for EGF Induction of Cell Proliferation in Gastric RGM1 Cells

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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.

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Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Medicine, Osaka City University, Osaka, 545-8585, Japan

    Eiji Sasaki, Kazunari Tominaga, Toshio Watanabe, Yasuhiro Fujiwara, Nobuhide Oshitani, Takayuki Matsumoto, Kazuhide Higuchi & Tetsuo Arakawa

  2. DVA Medical Center Long Beach, Long Beach, California, 90822

    A. S. Tarnawski

  3. Department of Medicine, University of California, Irvine, Irvine, California, 92697, USA

    A. S. Tarnawski

Authors
  1. Eiji Sasaki
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  2. Kazunari Tominaga
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  3. Toshio Watanabe
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  4. Yasuhiro Fujiwara
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  5. Nobuhide Oshitani
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  6. Takayuki Matsumoto
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  7. Kazuhide Higuchi
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  8. A. S. Tarnawski
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  9. Tetsuo Arakawa
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Correspondence to Kazuhide Higuchi.

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Sasaki, E., Tominaga, K., Watanabe, T. et al. COX-2 Is Essential for EGF Induction of Cell Proliferation in Gastric RGM1 Cells. Dig Dis Sci 48, 2257–2262 (2003). https://doi.org/10.1023/B:DDAS.0000007860.87503.09

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  • DOI: https://doi.org/10.1023/B:DDAS.0000007860.87503.09

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