Molecular regions of BRCA proteins responsible for cancer suppression

2018 Fiscal Year Final Research Report

• 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
• Keywords: 中心体

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.

Free Research Field

分子腫瘍学

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。