Novel strategy for the treatment of highly malignant tumors

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07040
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Kitagawa Masanobu 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (10177834)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: DNA損傷 / MCM2 / apoptosis / 腫瘍

Outline of Final Research Achievements

We have clarified the prominent enhancement of DNA-damage induced apoptosis in highly malignant tumor cells that showed strong expression of MCM2. To confirm the effect of MCM2 expression on the induction of DNA-damage induced apoptosis, we analyzed the apoptosic nature of highly malignant tumor cells after DNA-damage. As a result, we could show the strong expression of MCM2 in highly malignant tumors and the apoptosis-sensitive character of these tumors after DNA-damage.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

通常とは全く異なる新たな経路で p53 依存性アポトーシスシグナルが増強されていることが明らかになった。またin vitro の実験系を用いてこの現象の機序を徹底解明したところ、新たな apoptosis 誘導経路に関わる MCM2minochromosome maintenance protein 2） の作用機構の全貌を解明することができた。細胞株を用いた in vitro 実験系やマウスモデルを用いた in vivo 実験でMCM2高発現腫瘍にはDNA損傷に伴う強い apoptosdis 誘導が認められ、今後の治療開発を考える上で有用であると考えられた。