Analysis of the signals induced by the variant isoforms of TrkB expressed on ovarian clear cell adenocarcinoma

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11298
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Tokai University
• Principal Investigator: GOTO Yumiko 東海大学, 医学部, 助教 (50624574)
• Co-Investigator(Kenkyū-buntansha): 亀谷 美恵 東海大学, 医学部, 准教授 (50338787) ; 石本 人士 東海大学, 医学部, 教授 (10212937)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 卵巣癌 / 卵巣明細胞腺癌 / 神経栄養因子受容体TrkB / アイソフォーム

Outline of Final Research Achievements

Ovarian epithelial adenocarcinoma is comprised of four major pathological types; serous, endometrioid, mucinous and clear cell ovarian cancer (CCOC). Of those types, CCOC is the most resistant to chemotherapy, and its prognosis is poor. In Japan, the incidence rate of CCOC is more than 20% of ovarian cancer. We focused on Tropomyosin-related kinase B receptor (TrkB) which is expressed abundantly in ovary and the overexpression has been reported in various cancer types.
We confirmed that TrkB is expressed in CCOC and that the full length TrkB isoform, which has tyrosine kinase (TK) domain at intracellular region, highly expressed in progressive cases of CCOC. CCOC cell lines with TK domain upregulated the sensitivity to cisplatin if TK activity was inhibited by TK inhibitor K252a, suggesting the TK domain affects the survival of CCOC.

Free Research Field

産婦人科

Academic Significance and Societal Importance of the Research Achievements

卵巣明細胞腺癌は、予後が悪く、日本人に多い卵巣癌であるが、その発症機構は明らかではない。本研究では、TrkBという神経の生存維持に関わる分子が卵巣明細胞腺癌に発現していること、また、その中でもチロシンキナーゼ部位を持つ完全長型TrkBアイソフォームの発現が悪性度の高いケースで高率にみられることを明らかにした。チロシンキナーゼ分子を阻害する薬剤の存在下で培養すると、この分子を持つ卵巣明細胞腺癌の細胞株は抗がん剤耐性が低下したことから、今後、完全長型TrkBアイソフォームをターゲットとするような治療法の開発の可能性が期待される。