Activation of Wnt signaling through PGE2 induction in gastric tumorigenesis

2008 Fiscal Year Final Research Report

• Project/Area Number: 19390111
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kanazawa University
• Principal Investigator: OSHIMA Masanobu Kanazawa University, がん研究所, 教授 (40324610)
• Co-Investigator(Kenkyū-buntansha): OSHIMA Hiroko 金沢大学, がん研究所, 助教 (80362515)
• Co-Investigator(Renkei-kenkyūsha): OSHIMA Hiroko 金沢大学, がん研究所, 助教 (80362515)
• Project Period (FY): 2007 – 2008
• Keywords: Wnt / PGE2 / 胃がん / マウスモデル / 炎症

Research Abstract

遺伝子変異によるWntシグナルの恒常的亢進は胃がん発生の原因として知られている。一方、腫瘍組織では炎症性プロスタグランジンであるPGE2 の産生が誘導され、発がんを促進している。本研究では、胃がん発生におけるWnt シグナルとPGE2 経路の相互作用について解析を行ない、PGE2 依存的に発生する炎症反応がマクロファージからのTNF-α産生を誘導し、TNF-αが胃がん細胞のWnt シグナル亢進に作用して発がんを促進する可能性を初めて明らかにた。

Research Products

• [Journal Article] Induction of prostaglandin E2 pathway promotes gastric hamartoma development with suppression of bone morphogenetic protein signaling (2009)
  • Author(s): Oshima H, Itadani H, Kotani H, Oshima M
  • Journal Title: Cancer Res 69 Pages: 2729-2009
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase 7 is required for tumor formation, but dispensable for invasion and fibrosis in SMAD4 deficient intestinal adenocarcinomas (2009)
  • Author(s): Kitamura T, Biyajima K, Aoki M, (他2名)
  • Journal Title: Lab Invest 89 Pages: 98-105
  • Peer Reviewed
• [Journal Article] Stromal fiboblasts activated by tumor cells promote angiogenesis in mouse gastric cancer (2008)
  • Author(s): Guo X, Oshima H, Kitamura T, (他2名)
  • Journal Title: JBiol Chem 283 Pages: 19864-19871
  • Peer Reviewed
• [Journal Article] Activated macrophages promote Wnt signaling through tumor necrosis factor-α in gastric tumor cell (2008)
  • Author(s): Oguma K, Oshima H, Aoki M, (他7名)
  • Journal Title: EMBO J 27 Pages: 1671-1681
  • Peer Reviewed
• [Journal Article] The interleukin-6 family cytokine interleukin-11 regulates homeostatic epithelial cell turnover and promotes gastric tumor development (2008)
  • Author(s): Howlett M, Giraud A, Lescesen H (他11名, 12および13 番め)
  • Journal Title: Gastroenterology 136 Pages: 967-977
  • Peer Reviewed
• [Journal Article] Roles of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression and β-catenin activation in gastric carcinogenesis in N-methyl-N-nistrosourea-treated K19-C2mE transgenic mice (2008)
  • Author(s): Takasu S, Tsukamoto T, Cao XY, (他9名)
  • Journal Title: Cancer Sci 99 Pages: 2356-2364
  • Peer Reviewed
• [Journal Article] Blocking TNF-α in mice reduces colorectal carcinogenesis associated with chronic colitis (2008)
  • Author(s): Popivanova BK, Kitamura K, Wu Y, (他6名)
  • Journal Title: J Clin Invest 118 Pages: 560-580
  • Peer Reviewed
• [Journal Article] Platelet 12-lipoxigenase accelerates tumor promotion of mouse epidermal cells through enhancement of cloning efficiency (2008)
  • Author(s): Piao YS, Du YC, Oshima H, (他4名)
  • Journal Title: Carcinogenesis 29 Pages: 440-447
  • Peer Reviewed
• [Journal Article] Increased level of serum vascular endothelial growth factor by long-term exposure to hypergravity (2007)
  • Author(s): Oshima M, Suzuki H, Guo X, Oshima H
  • Journal Title: Exp Anim 56 Pages: 309-313
  • Peer Reviewed
• [Journal Article] Chromosomal instability by β-catenin/TCF transcription in APC or β-catenin mutant cells (2007)
  • Author(s): Aoki K., Aoki M., Sugai M. (他10名)
  • Journal Title: Oncogene 26 Pages: 3511-3520
  • Peer Reviewed
• [Journal Article] Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes (2007)
  • Author(s): Kawada K., Hosogi H, Sonoshita M, (他7名)
  • Journal Title: Oncogene 26 Pages: 4679-4622
  • Peer Reviewed
• [Journal Article] SMAD4-deficient intestinal recruit CCR1(+) myeloid cells that promote invasion (2007)
  • Author(s): Kitamura T, Kometani K, Matsunaga A,( 他8名)
  • Journal Title: Nat Genet 39 Pages: 467-475
  • Peer Reviewed
• [Journal Article] Suppression of tumulin polymerization by the LKB1-MAPK signaling (2007)
  • Author(s): Kojima Y, Miyoshi H, Clevers HC, Oshima M, (他2名)
  • Journal Title: J Biol Chem 282 Pages: 23532-23540
  • Peer Reviewed
• [Presentation] Inflammation accelerates tumorigenesis through promotion of Wnt signaling (2008)
  • Author(s): Oshima M
  • Organizer: 67th Annual Meeting for Japanese Cancer Association[日本癌学会学術総会]
  • Place of Presentation: Nagoya
  • Year and Date: 20081000
• [Presentation] Gastric tumorigenesis through EGFR activation in Wnt and PGE2 transgenic mice (2008)
  • Author(s): Oshima H, Oguma K, Kotani H, and Oshima M
  • Organizer: 67th Annual Meeting for Japanese Cancer Association[日本癌学会学術総会]
  • Place of Presentation: Nagoya
  • Year and Date: 20081000
• [Presentation] Promotion of Wnt signaling by activated macrophage-derived TNF-α (2008)
  • Author(s): Oguma K, Oshima H, Aoki M, (他7名)
  • Organizer: 67th Annual Meeting for Japanese Cancer Association[日本癌学会学術総会]
  • Place of Presentation: Nagoya
  • Year and Date: 20081000
• [Presentation] Inflammatory responses accelerate Wnt signaling in gastric epithelial cells (2008)
  • Author(s): Oshima M, Oshima H, Oguma K, (他2名)
  • Organizer: 99th Annual Meeting of American Association for Cancer Research (AACR)
  • Place of Presentation: San Diego
  • Year and Date: 20080400
• [Presentation] 新規モデルマウスを用いた胃がん発生分子機序の解析 (2008)
  • Author(s): 大島正伸
  • Organizer: 第97回日本病理学会
  • Place of Presentation: 金沢
  • Year and Date: 2008-05-16
• [Presentation] Novel gastric cancer mouse model by transgenic expression of Wnt1 and prostaglandin E2 (2007)
  • Author(s): Oshima H, Taketo MM, Oshima M.
  • Organizer: 12th Korea-Japan Cancer Research Workshop
  • Place of Presentation: Sapporo
  • Year and Date: 2007-12-22
• [Presentation] Gastric tumorigenesis through Wnt signaling and host inflammatory responses (2007)
  • Author(s): Oshima M, Oguma K, Oshima H.
  • Organizer: 12th Korea-Japan Cancer Research Workshop
  • Place of Presentation: Sapporo
  • Year and Date: 2007-12-22
• [Presentation] 皮膚表皮JB6P+細胞の形質転換における12-リポキシゲナーゼの促進作用 (2007)
  • Author(s): 朴英実, 杜宇〓, 大島浩子, (他4名)
  • Organizer: 第30回日本分子生物学会第80回日本生化学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] 消化器がん発生におけるPGE2とマクロファージの役割の解析 (2007)
  • Author(s): 大島正伸
  • Organizer: 第30回日本分子生物学会第80回日本生化学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] 活性化マクロファージによるWntシグナルの亢進 (2007)
  • Author(s): 小熊圭祐, 大島浩子, 仲一仁, 平尾敦, 大島正伸
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] WntシグナルとPGE2経路の活性化による胃がん発生モデルマウス (2007)
  • Author(s): 大島正伸, 大島浩子, 武藤誠
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] WntシグナルとCOX-2/PGE2経路の相互作用による消化器発がん (2007)
  • Author(s): 大島正伸
  • Organizer: 第25回日本ヒト細胞学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2007-08-04
• [Presentation] JB6P+細胞の形質転換における12-リポキシゲナーゼの役割 (2007)
  • Author(s): 朴英実, 吉本谷博, 大島正伸
  • Organizer: 第49回日本脂質生化学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-06-05
• [Presentation] Mouse model of gastric cancer by simultaneous activation of Wnt and PGE2 pathways (2007)
  • Author(s): Oshima M, Oshima H, Taketo MM.
  • Organizer: Annual Meeting of American Association for Cancer Research (AACR)
  • Place of Presentation: Los Angeles
  • Year and Date: 2007-04-18
• [Book] by Wang TC. et.al. Springer (2008)
  • Author(s): Oshima M, Oshima H, and Taketo MM
  • Total Pages: 513-540
  • Publisher: Prostaglandin and transforming growth factor-β signaling in gastric cancer. In The Biology of Gastric Cancers, Eds