The significance of prostaglandin in epithelial-mesenchymal transition in pathophysiology of gastrointestinal disease

• Project/Area Number: 19790493
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Osaka City University
• Principal Investigator: TANIGAWA Tetsuya Osaka City University, 大学院・医学研究科, 講師 (70423879)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,360,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2008: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2007: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: 上皮―間充織形質転換 / プロスタグランジン / 15-hydroxyprostaglandin dehydrogenase / 創傷治癒 / 胃癌 / 上皮-間充織形質転換 / 上皮-間充織形転換 / 15-hdroxrostalandin dehydroenase / E-cadherin / a-smooth muscle actin / restitution

Research Abstract

Prostaglandin (PG) plays an important role in gastrointestinal wound healing and carcinogenesis by enhancing cell proliferation, migration, invasion and metastasis. In the preliminary study for the research of epithelial to mesenchymal transition (EMT) and PG in pathophysiology of gastrointestinal disease, we investgated the alteration of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in gastric cancer and gastric ulcer.
1. We determined the correlations between pattern of expression of 15-PGDH in gastric adenocarcinoma and various clinicopathological factors and patient outcome. In 35 of 71 cases of gastric adenocarcinoma, expression of 15-PGDH protein was reduced in tumor tissues. Multivariate analysis revealed reduction of 15-PGDH expression to be an independent predictor of poor survival.
2. We investigated the expression of 15-PGDH in the stomach and acetic acid-induced gastric ulcer in mice and the mechanism by which 15-PGDH is regulated during gastric ulcer healing. Expression of mRNA for PGDH was reduced by 57% compared with normal tissue. Consistent with this, protein level of 15-PGDH in ulcer tissue was decreased compared with that in normal tissue. Epidermal growth factor receptor (EGFR) kinase inhibitor reversed the down-regulation of mRNA expression of 15-PGDH in ulcer tissue.

Research Products

• [Journal Article] Reduction of 15-hydroxyprostaglandin dehydrogenase expression is an independent predictor of poor survival associated with enhanced cell proliferation in gastric adenocarcinoma (2010)
  • Author(s): Tatsuwaki H, Tanigawa T, Watanabe T, Machida H, Okazaki H, Yamagami H, Shiba M, Watanabe K, Tominaga K, Fujiwara Y, Oshitani N, Muguruma K, Sawada T, Hirakawa K, Higuchi K, Arakawa T
  • Journal Title: Cancer Sci. 101(2) Pages: 550-8
  • Peer Reviewed
• [Journal Article] 【消化器疾患の病態生理】胃癌における15-Hydroxyprostaglandin Dehydrogenaseの意義 (2010)
  • Author(s): 達脇大, 谷川徹也, 渡辺俊雄, 町田浩久, 岡崎博俊, 山上博一, 斯波将次, 渡辺憲治, 富永和作, 藤原靖弘, 押谷伸英, 六車和也, 澤田鉄二, 平川弘聖, 樋口和秀, 荒川哲男
  • Journal Title: Progress in Medicine 30巻3号 Pages: 791-796
• [Journal Article] Reduction of 15-hydroxyprostaglandin dehydrogenase expression is an in dependent predictor of poor survival associated with enhanced cell proliferation in gastric adenocarcinoma. (2010)
  • Author(s): Hiroshi Tatsuwaki, et al.
  • Journal Title: Cancer Science 101 Pages: 550-558
  • Peer Reviewed
• [Journal Article] 胃潰瘍治癒過程におけるプロスタグランジン代謝酵素15-hydroxyprostaglandin dehydrogenaseの発現動態とその調節因子 (2009)
  • Author(s): 谷川徹也, 渡辺俊雄, 達脇大, 岡崎博俊, 富永和作, 藤原靖弘, 押谷伸英, 荒川哲男
  • Journal Title: 潰瘍 36巻1号 Pages: 87-90
  • NAID: 10025371647
• [Journal Article] 胃潰瘍治癒過程におけるプロスタグランジン代謝酵素15-hydroxyprostaglandin dehydrogenaseの発現動態とその調節因子 (2009)
  • Author(s): 谷川徹也, 他
  • Journal Title: 潰瘍 36 Pages: 87-90
  • NAID: 10025371647
• [Presentation] 消化器疾患における分子腫瘍マーカーの新展開胃癌における15-Hydroxyprostaglandin dehydrogenaseの発現低下は独立予後不良予測因子である (2010)
  • Author(s): 谷川徹也, 達脇大, 渡辺俊雄
  • Organizer: 第96回日本消化器病学会総会
  • Place of Presentation: 新潟
  • Year and Date: 2010-04-24
• [Presentation] Down-regulation of 15-Hydroxyprostaglandin Dehydrogenase During Gastric Ulcer Healing (2009)
  • Author(s): Tanigawa T, Tatsuwaki H, Watanabe T, Machida H, Okazaki H, Yamagami H, Watanabe K, Tominaga K, Fujiwara Y, Higuchi K, Arakawa T.
  • Organizer: The 109th Annual Meeting of the AGA
  • Place of Presentation: Chicago, USA
  • Year and Date: 2009-05-30
• [Presentation] 胃癌の細胞増殖に対する15-Hydroxyprostaglandin dehydrogenaseの意義 (2009)
  • Author(s): 達脇大、谷川徹也、渡辺俊雄、岡崎博俊、富永和作、藤原靖弘、押谷伸英、荒川哲男
  • Organizer: 第95回日本消化器病学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2009-05-07
• [Presentation] 胃潰瘍治癒過程におけるプロスタグランジン代謝酵素 : 15-hydroxyprostaglandin dehydrogenaseの発現動態とその規定因子 (2009)
  • Author(s): 谷川徹也, ほか
  • Organizer: 第5回日本消化管学会
  • Place of Presentation: 東京
  • Year and Date: 2009-02-13
• [Presentation] 胃癌の細胞増殖に対する15-hydroxyprostaglandin dehydrogenaseの意義 (2009)
  • Author(s): 達脇大, 谷川徹也, 渡辺俊雄, 岡崎博俊, 富永和作, 藤原靖弘, 押谷伸英, 荒川哲男
  • Organizer: 第5回日本消化管学会総会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-02-12
• [Presentation] 胃潰瘍治癒過程におけるプロスタグランジン代謝酵素:15-hydroxyprostaglandin dehydrogenaseの発現動態について (2009)
  • Author(s): 谷川徹也, 達脇大, 渡辺俊雄, 岡崎博俊, 富永和作, 藤原靖弘, 押谷伸英, 荒川哲男
  • Organizer: 第5回日本消化管学会総会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2009-02-12
• [Presentation] 胃癌の細胞増殖に対する15-Hydroxyprostaglandin dehydrogenaseの意義 (2009)
  • Author(s): 達脇大, ほか
  • Organizer: 第5回日本消化管学会
  • Place of Presentation: 東京
  • Year and Date: 2009-02-12
• [Presentation] 胃潰瘍治癒過程におけるプロスタグランジン代謝酵素 : 15-ydroxyprostaglandin dehydrogenaseの発現動態について (2008)
  • Author(s): 谷川徹也, ほか
  • Organizer: 第36回日本潰瘍学会
  • Place of Presentation: 北海道
  • Year and Date: 2008-09-06
• [Presentation] 胃潰瘍治癒過程におけるプロスタグランジン代謝酵素:15-hydroxyprostaglandin dehydrogenaseの発現動態について (2008)
  • Author(s): 谷川徹也, 達脇大, 渡辺俊雄, 岡崎博俊, 富永和作, 藤原靖弘, 押谷伸英, 荒川哲男
  • Organizer: 第36回日本潰瘍学会
  • Place of Presentation: 北海道
  • Year and Date: 2008-09-05
• [Presentation] Loss of 15-hydroxyprostaglandin dehydrogenase expression is associated with cancer cell proliferation and poor prognosis in gastric cancer (2008)
  • Author(s): 達脇大, ほか
  • Organizer: アメリカ消化器病週間(DDW)
  • Place of Presentation: サンディエゴ(アメリカ合衆国)
  • Year and Date: 2008-05-18
• [Presentation] Tetuso Arakawa Loss of 15-hydroxyprostaglandin dehydrogenase expression is associated with cancer cell proliferation and poor prognosis in gastric cancer (2008)
  • Author(s): Hiroshi Tatsuwaki, Tetsuya Tanigawa, Toshio Watanabe, Hirohisa Machida, Hirotoshi Okazaki, Masatsugu Shiba, Kazunari Tominaga, Yasuhiro Fujiwara, Nobuhide Oshitani, Kazuya Muguruma, Tetsuji Sawada, Kosei Hirakawa, Kazuhide Higuchi
  • Organizer: The 108th Annual Meeting of the AGA
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-05-17
• [Presentation] 胃癌組織における15-Hydroxyprostaglandin dehydrogenaseの発現動態の検討 (2008)
  • Author(s): 達脇大, 谷川徹也, 渡辺俊雄, 町田浩久, 岡崎博俊, 斯波將次, 富永和作, 藤原靖弘, 押谷伸英, 六車一哉, 澤田鉄二, 平川弘聖, 樋口和秀, 荒川哲男
  • Organizer: 第94回日本消化器病学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-05-09
• [Presentation] 胃癌における15-Hydroxyprostaglandin Dehydrogenaseの発現動態とその意義 (2008)
  • Author(s): 達脇大, 谷川徹也, 渡辺俊雄, 町田浩久, 岡崎博俊, 斯波將次, 富永和作, 伊倉義弘, 藤原靖弘, 押谷伸英, 六車一哉, 澤田鉄二, 平川弘聖, 樋口和秀, 荒川哲男
  • Organizer: 第4回日本消化管学会総会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2008-02-07