Unveil aggravating factors and their molecular mechanisms in endometrial cancer using mouse model with uterine-specific Pten deletion

• Project/Area Number: 16H05470
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kanazawa University
• Principal Investigator: Daikoku Takiko 金沢大学, 学際科学実験センター, 教授 (30767249)
• Co-Investigator(Kenkyū-buntansha): 藤原 浩 金沢大学, 医学系, 教授 (30252456) ; 寺川 純平 金沢大学, 学際科学実験センター, 助教 (90777731) ; 高倉 正博 金沢大学, 附属病院, 准教授 (20313661)
• Research Collaborator: HORIKE Shinichi ; IIZUKA Takashi ; MATSUOKA Ayumi ; OBATA Takeshi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
• Keywords: マウスモデル / 子宮体癌 / 子宮がん / Pten

Outline of Final Research Achievements

Using our new endometrial cancer mouse models, we found that the Pten in uterine stroma represses malignant transformation of Pten null uterine epithelium. We further demonstrated that Pten in uterine epithelium is essential to repress uterine stromal sarcoma in mouse model. We also found some aggravating factors for endometrial cancer initiation and progression in this study.

Academic Significance and Societal Importance of the Research Achievements

本研究で得られた子宮がん発生への周辺組織の影響および卵巣ホルモンの子宮がん発生・進行への関与はこれまでの常識を覆す結果を含んでおり、学術的意義がある。また、本研究で新たに発見された子宮体癌発生・進行を促進する憎悪因子は、子宮体癌の新たな治療ターゲットとなり、新規治療薬の開発につながると考えられ、社会的意義がある。

Research Products

• [Int'l Joint Research] Ohio State University/Cincinnati Children's Hospital(米国)
• [Journal Article] Ovarian-innsufficiency and CYNNB1 mutations drive malignant transformation of endometrial hyperplasia with altered PTEN/PI3K activities. (2019)
  • Author(s): Terakawa J, Serna VA, Taketo MM, Daikoku T, Suarez AAA, Kurita T.
  • Journal Title: PNAS Volume: 印刷中 Issue: 10 Pages: 4528-4537
  • DOI: 10.1073/pnas.1814506116
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The uterine epithelial loss of Pten is inefficient to induce endometrial cancer with intact stromal Pten. (2018)
  • Author(s): Liang X, Daikoku T, Terakawa J, Ogawa Y, Joshi AR, Ellenson LH, Sun X, Dey SK.
  • Journal Title: PLoS Genetics Volume: 14 Issue: 8 Pages: e1007630-e1007630
  • DOI: 10.1371/journal.pgen.1007630
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Crosstalk between PKCαand PI3K/AKT signaling is tumor suppressive in the endometrium. (2018)
  • Author(s): Hsu AH, Lum MA, Shim KS, Frederick PJ, Morrison CD, Chen B, Lele SM, Sheinin YM, Daikoku T, Dey SK, Leone G, Black AR, Black JD
  • Journal Title: Cell Report Volume: 24 Issue: 3 Pages: 655-669
  • DOI: 10.1016/j.celrep.2018.06.067
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] マウスモデルからみる子宮疾患 (2017)
  • Author(s): 大黒多希子
  • Organizer: 第５３回北陸生殖医学会学術講演会
  • Invited
• [Presentation] マウスモデルを用いた子宮疾患の解析 (2017)
  • Author(s): 大黒多希子
  • Organizer: 第５８回日本組織細胞科学会・シンポジウム
  • Invited
• [Presentation] 子宮で発症する癌とPtenの関係 (2017)
  • Author(s): 大黒多希子
  • Organizer: 第２７回腫瘍病理セミナー
  • Invited
• [Presentation] マウスモデルを用いた子宮疾患の解析 (2016)
  • Author(s): 大黒多希子
  • Organizer: 第６２回日本病理学会 秋季特別総会
  • Place of Presentation: 金沢市 ニューグランドホテル
  • Year and Date: 2016-11-11
  • Invited