Molecular regions of BRCA proteins responsible for cancer suppression

Research Project

Project/Area Number	15K06833
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Tumor biology
Research Institution	Kanagawa Cancer Center Research Institute
Principal Investigator	Takenaka Katsuya 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), その他部局等, 技師・研究員 (20378706)
Co-Investigator(Kenkyū-buntansha)	荻朋男名古屋大学, 環境医学研究所, 教授 (80508317)
Project Period (FY)	2015-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000) Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	中心体 / 分子内責任部位 / 低酸素 / 遺伝子破壊 / 画像認識 / タンパク質間相互作用
Outline of Final Research Achievements	BRCA2 germline mutations account for the majority of heredity breast and ovarian cancer. A major function of BRCA2 is known as a regulator of homologous recombination in DNA damage repair. In addition, BRCA2 also plays an important role in centrosomal regulation, whose dysfunction might be involved inthe tumorigenesis of breast cancer. Though, detail molecular mechanism was not uncovered. In the present study, we tried to locate a molecular region of BRCA2 responsible for this function. Numbers of centrosome in a cell are counted to see if an overexpression of a specific fragment of BRCA proteins could impair a numerical integrity of centrosomes. For this purpose we developed an automated centrosome-counting system based on image recognition, which allows us to judge a large number of transfected cells without human bias.
Academic Significance and Societal Importance of the Research Achievements	比較的小型で発現量も多い分子については多種多様な生化学・細胞生物学的手法によって解析が進んできたが，BRCAのような発現量の少ない超巨大分子については実験手法の制約により分子機構が臨床応用可能なレベルにまで解明されていない。そのため画期的な解析手法の導入と独創的な定量法の開発により，これまで解析が回避されてきた超巨大分子についても効率良く高精度なスクリーニングを可能にした。治療につながる開発標的を見出す標準の確立により癌診断・治療に強く波及し得ることから国民の要請に応えられる。