Role of prostaglandin terminal synthases in chemical carcinogen-induced carcinogenesis

• Project/Area Number: 25860100
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Showa University
• Principal Investigator: SASAKI Yuka 昭和大学, 薬学部, 助教 (40635108)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 化学発がん / プロスタグランジン / mPGES-1 / PGIS / がん

Outline of Final Research Achievements

Prostaglandin (PG) I2 synthase (PGIS) and Microsomal PGE synthase-1 (mPGES-1) are PG terminal synthases that function downstream of inducible COX-2 in the PGI2 and PGE2 biosynthetic pathway, respectively. In this study, we used mice deficient in PGIS and mPGES-1 to examine the importance of these PG terminal synthases in chemical carcinogen-induced carcinogenesis.
This study indicate that mPGES-1-derived PGE2 and PGIS-derived PGI2 have opposing effects on chemical-induced colon carcinogenesis. Namely, the former PGE2 promotes and exacerbates chemical carcinogenesis, while the latter PGI2 suppresses it.

Research Products

• [Journal Article] Role of long-chain acyl-coenzyme A synthetases in the regulation of arachidonic acid metabolism in interleukin 1β-stimulated rat fibroblasts (2014)
  • Author(s): Kuwata, H., Yoshimura, M., Sasaki, Y., Yoda, E., Nakatani, Y., Kudo, I., Hara, S.
  • Journal Title: Biochimica et Biophyica Acta - Molecular and Cell Biology of Lipids Volume: 1841 Issue: 1 Pages: 44-53
  • DOI: 10.1016/j.bbalip.2013.09.015
  • Peer Reviewed
• [Presentation] 膜結合型プロスタグランジンE合成酵素の皮膚発がんへの関与の解析 (2015)
  • Author(s): 会田 衣利,佐々木 由香,蛭田 凌平, 原 俊太郎
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] Role of microsomal prostaglandin E synthase-1 in chemical-induced carcinogenesis (2015)
  • Author(s): Yuka Sasaki, Shuntaro Hara
  • Organizer: 6th international conference on Phospholipase A2 and Lipid Mediators (PLM2015)
  • Place of Presentation: 東京
  • Year and Date: 2015-02-10 – 2015-02-12
• [Presentation] Prostacyclin synthase deficiency suppressed obesity in mice (2014)
  • Author(s): YUKA SASAKI, Moe Akatsu, Yuri Yamakawa, Chieko Yokoyama, Shuntaro Hara
  • Organizer: 5th European Workshop on Lipid Mediators
  • Place of Presentation: Istanbul
  • Year and Date: 2014-10-23 – 2014-10-24
• [Presentation] 脂肪蓄積におけるプロスタサイクリン合成酵素の機能の解析 (2014)
  • Author(s): 佐々木由香、山川友理、赤津萌、横山知永子、原俊太郎
  • Organizer: 日本薬学会第134年回
  • Place of Presentation: 熊本
• [Presentation] Genetic deletion of prostacyclin synthase, a cyclooxygenase 2 downstream enzyme, in mice promotes carcinogenesis in contrast to that of microsomal prostaglandin E synthase-1 (2013)
  • Author(s): Shuntaro Hara, Yuka Sasaki
  • Organizer: 13th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases
  • Place of Presentation: Puerto Rico, USA
• [Presentation] Effect of gene deletion of two prostaglandin terminal synthases, PGIS and mPGES-1 on adiposity in mice (2013)
  • Author(s): Yuka Sasaki, Moe Akatsu, Yuri Yamakawa, Chieko Yokoyama, Shuntaro Hara
  • Organizer: 13th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases
  • Place of Presentation: Puerto Rico, USA
• [Presentation] プロスタグランジン最終合成酵素PGISおよびmPGES-1の肥満への関与 (2013)
  • Author(s): 佐々木由香、赤津萌、山川友理、横山知永子、原俊太郎
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Book] 遺伝子医学MOOK24号 (2013)
  • Author(s): 佐々木由香、原俊太郎
  • Publisher: メディカル・ドゥ