Functional analysis of MLL complex in solid tumor progression

• Project/Area Number: 17K08662
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Nagasaki University
• Principal Investigator: YONEDA Mitsuhiro 長崎大学, 医歯薬学総合研究科(医学系), 講師 (80508367)
• Co-Investigator(Kenkyū-buntansha): 伊藤 敬 長崎大学, 医歯薬学総合研究科(医学系), 教授 (90306275)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: がん / 複合体 / 癌

Outline of Final Research Achievements

The cells stably expressing MEN1 or BRD4 which are already known as subunits of the MLL complex were established. MLL complex without MLL mutation was purified. Further, MLL-mutated colon cancer cells stably expressing subunit of the MLL complex were also established.
Knockdown experiments in HeLa cells revealed that subunits of the MLL complex have an important role in solid tumor proliferation.
The extract which includes a candidate molecule for disruption of MLL complex formation was identified by a developed screening assay, in order to obtain knowledge which is served as a foundation for the discoveries of early diagnosis, prognosis and more effective molecular targets for MLL-mutated solid tumors.

Academic Significance and Societal Importance of the Research Achievements

MLL遺伝子変異を有するMLL複合体に特異的な構成因子やMLL複合体形成を阻害する薬剤が発見された場合、MLL遺伝子異常を有する固形癌患者の早期診断・予後診断や、より有効な分子標的療法の発見につながる礎となる知見が得られる。