Role and regulation of sex steroid synthesis key enzyme:CYP17 in endometrial cancer

• Project/Area Number: 17K11266
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Tohoku University
• Principal Investigator: ITO Kiyoshi 東北大学, 災害科学国際研究所, 教授 (70241594)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 子宮内膜癌 / CYP17 / androgen / estrogen / DHEA / androgen receptor / endometrial cancer / endometrial carcinoma / 癌 / 性ステロイド合成酵素 / アンドロゲン / エストロゲン

Outline of Final Research Achievements

Endometrial cancer is known to have a hormone-dependent growth. Abiraterone, a hormone synthase CYP17 inhibitor, is used as a hormone therapy drug for prostate cancer patients. In this study, we clarified the significance of CYP17 in endometrial cancer and found that abiraterone may also be effective in endometrial cancer. CYP17 are expected as new hormone therapeutic target for endometrial cancer.

Academic Significance and Societal Importance of the Research Achievements

子宮内膜癌の術後補助療法として副作用の少ないホルモン療法が望まれますが、代表的な黄体ホルモン療法を含めてその効果は明確ではありません。しかし様々な研究から子宮内膜癌はホルモン依存性に増殖することは明らかであるため、さらなるホルモン療法に関する研究の発展が望まれてきました。本研究では、CYP17の子宮内膜癌での意義を初めて明らかにすることができ（学術的意義）、さらに既存の前立腺癌ホルモン療法剤が子宮内膜癌に対しても有効である可能性を示すことができました(社会的意義)。

Research Products

• [Journal Article] Multiple primary cancers associated with endometrial and ovarian cancers: An analysis based upon the Japan Autopsy Annual Database from 2002 to 2010. (2019)
  • Author(s): Miki Y, Sugawara Y, Shibahara Y, Tsuji I, Sasano H, Ito K.
  • Journal Title: J Obstet Gynaecol Res. Volume: 45 Issue: 5 Pages: 1012-1018
  • DOI: 10.1111/jog.13934
  • Peer Reviewed / Open Access
• [Journal Article] 17β-Hydroxysteroid Dehydrogenase Type 2 Expression Is Induced by Androgen Signaling in Endometrial Cancer. (2018)
  • Author(s): Hashimoto C, Miki Y, Tanaka S, Takagi K, Fue M, Doe Z, Li B, Yaegashi N, Suzuki T, Ito K.
  • Journal Title: Int J Mol Sci. Volume: 19 Issue: 4 Pages: 1139-1152
  • DOI: 10.3390/ijms19041139
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Relaxin 2/RXFP1 Signaling Induces Cell Invasion via the β-Catenin Pathway in Endometrial Cancer. (2018)
  • Author(s): Fue M, Miki Y, Takagi K, Hashimoto C, Yaegashi N, Suzuki T, Ito K.
  • Journal Title: International Journal of Molecular Sciences Volume: 19 Issue: 8 Pages: 2438-2450
  • DOI: 10.3390/ijms19082438
  • Peer Reviewed / Open Access
• [Journal Article] Exploring Protein-Protein Interaction in the Study of Hormone-Dependent Cancers. (2018)
  • Author(s): Miki Y, Iwabuchi E, Ono K, Sasano H, Ito K.
  • Journal Title: International Journal of Molecular Sciences Volume: 19 Issue: 10 Pages: 3173-3173
  • DOI: 10.3390/ijms19103173
  • Peer Reviewed / Open Access
• [Journal Article] Retinoic acid receptor beta: a potential therapeutic target in retinoic acid treatment of endometrial cancer (2017)
  • Author(s): Tsuji K, Utsuomiya H, Miki Y, Hanihara M, Fue M, Takagi K, Nishimoto M, Suzuki F, Yaegashi N, Suzuki T, Ito K
  • Journal Title: Internatioal Journal of Gynecologic Cancer Volume: 印刷中 Issue: 4 Pages: 643-650
  • DOI: 10.1097/igc.0000000000000995
  • Peer Reviewed / Open Access
• [Journal Article] Roles of Aryl Hydrocarbon Receptor in Aromatase-Dependent Cell Proliferation in Human Osteoblasts (2017)
  • Author(s): Miki Yasuhiro、Hata Shuko、Ono Katsuhiko、Suzuki Takashi、Ito Kiyoshi、Kumamoto Hiroyuki、Sasano Hironobu
  • Journal Title: International Journal of Molecular Sciences. Volume: 18 Issue: 10 Pages: 2159-2159
  • DOI: 10.3390/ijms18102159
  • Peer Reviewed / Open Access
• [Presentation] 災害科学、災害医学、そしてホルモン―災害科学国際研究所での取り組みを中心に― (2019)
  • Author(s): 伊藤潔、三木康宏
  • Organizer: 第92回日本内分泌学会
  • Invited
• [Presentation] ホルモン依存性癌におけるホルモンシグナルの可視化 (2019)
  • Author(s): 三木康宏、岩渕英里奈、鈴木貴、笹野公伸、伊藤潔
  • Organizer: 第92回日本内分泌学会
• [Presentation] 子宮内膜癌におけるステロイドホルモンとKruppel-like factor5の発現 (2019)
  • Author(s): 三木康宏、吉田伶奈、高木清司、鈴木貴、伊藤潔
  • Organizer: 第92回日本内分泌学会
• [Presentation] 子宮内膜癌発症機序と多嚢胞性卵巣症候群（PCOS） (2019)
  • Author(s): 伊藤潔
  • Organizer: 第43回日本女性栄養・代謝学会学術集会
  • Invited
• [Presentation] 子宮内膜癌組織におけるホルモン濃度とKruppel-like factor 5の発現 (2018)
  • Author(s): 三木康宏、吉田伶奈、高木清司、鈴木貴、伊藤潔
  • Organizer: 第19回ホルモンと癌研究会
• [Presentation] 子宮内膜癌におけるDehydroepiandrosterone(DHEA)の組織中濃度とその意義 (2018)
  • Author(s): 三木康宏、吉田伶奈、高木清司、鈴木貴、伊藤潔
  • Organizer: 第25回日本生殖内分泌学会
• [Presentation] 子宮内膜癌におけるDehydroepiandrosterone(DHEA)の意義 (2018)
  • Author(s): 三木康宏、吉田伶奈、高木清司、鈴木貴、伊藤潔
  • Organizer: 第24回東北内分泌研究会＆第36回日本内分泌学会東北地方会
• [Presentation] Intratumoral Steroid Hormone And Krüppel-Like Factor 5 Expression In Endometrial Cancer (2018)
  • Author(s): Miki Y, Fue M, Yoshida R, Shimizu M, Takagi K, Suzuki T, Ito K
  • Organizer: The Endocrine Society's 100th Annual Meeting & EXPO
  • Int'l Joint Research
• [Presentation] Intratumoral Level Of Dehydroepiandrosterone And Its Role In Endometrial Cancer Cell Proliferation (2018)
  • Author(s): Yoshida R, Miki Y, Fue M, Takahashi S, Takagi K, Suzuki T, Ito K
  • Organizer: The Endocrine Society's 100th Annual Meeting & EXPO
  • Int'l Joint Research
• [Presentation] The effect of dehydroepiandrosterone on the proliferation of endometrial cancer cells (2017)
  • Author(s): Yoshida R, Miki Y, Fue M, Takagi K, Suzuki T, Ito K
  • Organizer: 第76回日本癌学会学術総会