Is induction of TREX2 complex dysfunction a target for anticancer drug hypersensitivity?

• Project/Area Number: 16K15603
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: GONDO Naomi 愛知県がんセンター(研究所), 腫瘍免疫応答研究分野, 研究員 (30743356)
• Co-Investigator(Kenkyū-buntansha): 桑原 一彦 愛知県がんセンター(研究所), その他部局等, 客員研究員 (10263469) ; 葛島 清隆 愛知県がんセンター(研究所), 腫瘍免疫応答研究分野, 分野長 (30311442) ; 岩田 広治 愛知県がんセンター(研究所), がん予防研究分野, 研究員 (90295600)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 乳癌 / 薬剤抵抗性 / DSS1 / TREX2 / 薬剤感受性 / 医療

Outline of Final Research Achievements

It has been previously reported that decreased expression of DSS1, a component of the TREX2 complex, induces DNA instability and affects drug sensitivity. In this study, we analyzed whether the expression of DSS1/PCID2 protein as the TREX2 complex　similarly affects drug sensitivity and prognosis of breast cancer. The combined approach by in vitro analysis using breast cancer cell lines and breast cancer cohort analysis revealed that the expression of DSS1/PCID2 protein is involved in drug sensitivity and also affects the prognosis of breast cancer. These data suggested that the TREX2 component might be a new target to augment chemosensitivity.

Academic Significance and Societal Importance of the Research Achievements

乳癌治療において、癌の薬剤抵抗性は重要課題の一つである。今回我々は、乳癌細胞株、コホート研究の解析により薬物感受性に影響を与えるたんぱく質DSS1/PCID2(TREX2複合体の構成タンパク)を同定した。乳癌細胞株レベルでこれらのタンパク質の増減により、薬剤感受性が大きく変化することを明らかにした。治療抵抗性をもつ乳癌において、これらのタンパク質を新規のターゲットとする薬剤の開発の基盤になると研究であると考える。

Research Products

• [Presentation] Forced reduction of DSS1, a member of TREX2 complex, highly sensitizes chemotherapy to breast cancer cells in a BRCA2-independent manner. (2017)
  • Author(s): Kazuhiko Kuwahara, Naomi Gondo, Andri Rezano, Zhenhuan Zhang, Yukari Hato, Kiyotaka Kuzushima, Hiroji Iwata, Tatsuya Toyama, and Eisaku Kondo
  • Organizer: AACR Annual Meeting 2017
  • Place of Presentation: Washington, DC
  • Year and Date: 2017-04-01
  • Int'l Joint Research