Generation of a novel model to elucidate the function of BRCA2 mutations and binding molecules in tumors
| Project/Area Number |
18H02334
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 42020:Veterinary medical science-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
落合 和彦 日本獣医生命科学大学, 獣医学部, 准教授 (30550488)
安居院 高志 北海道大学, 獣医学研究院, 教授 (00212457)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2020: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | BRCA2 / Rad51 / 乳腺腫瘍 / 前立腺癌 / RAD51 / 腫瘍発症機構 / ゲノム不安定化 / 疾患モデル / 分子間相互作用 / アンドロゲン受容体 / PALB2 / ゲノム不安定 / BRCAl2 / p53 |
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| Outline of Final Research Achievements |
To elucidate the effects of the canine tumor suppressor protein BRCA2 on tumorigenesis, we focused on the regulation of BRCA2 expression, a group of binding molecules such as RAD51, and sex hormone receptor-related molecules.
Splicing variants of canine BRCA2 were found in tissues and cell lines, and similar variants were found in human cell lines. We have elucidated the effects of mutations in BRCA2 and its interacting molecules on the function of the gene. We compared the C-terminal RAD51-binding domain of canine and human BRCA2 and identified a core motif, and found that the C-terminal RAD51-binding domain of BRCA2 increased resistance to X-irradiation and mitomycin C treatment.
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| Academic Significance and Societal Importance of the Research Achievements |
イヌの獣医療において、乳腺腫瘍は雌イヌで全腫瘍の約半数を占めて発症頻度が高く、その約半数が悪性となる。本研究では、BRCA2スプライシングバリアントを調べ、イントロン１においてヒトとイヌで保存された配列にサイレンサーとして機能する領域があることを見出した。BRCA2のC末端RAD51結合ドメインの変異(S3323N)が機能的に中立であることや、BRCA2と相互作用するp53の変異による四量体形成不全がDNA損傷時の細胞周期や細胞死に影響すること等を示した。これらの知見は、イヌ乳腺腫瘍の獣医学等に有益な情報を提供すると考えられる。
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Report
(5 results)
Research Products
(20 results)
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[Journal Article] In vitro anticancer effects of alpelisib against PIK3CA-mutated canine hemangiosarcoma cell lines2022
Author(s)
Maeda M, Ochiai K, Michishita M, Morimatsu M, Sakai H, Kinoshita N, Sakaue M, Onozawa E, Azakami D, Yamamoto M, Ishioka K, Sadahira T, Watanabe M, Tanaka Y.
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Journal Title
Oncology Reports
Volume: 47
Issue: 4
Pages: 84-84
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The canine RAD51 mutation leads to the attenuation of interaction with PALB2.2019
Author(s)
Uemura M, Ochiai K, Morimatsu M, Michishita M, Onozawa E, Azakami D, Uno Y, Yoshikawa Y, Sasaki T, Watanabe M, Omi T.
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Journal Title
Veterinary and Comparative Oncology
Volume: -
Issue: 2
Pages: 1-9
DOI
Related Report
Peer Reviewed
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[Journal Article] Endogenous Leu332Gln mutation in p53 disrupts the tetramerization ability in a canine mammary gland tumor cell line.2018
Author(s)
Ochiai K, Azakami D, Morimatsu M, Hirama H, Kawakami S, Nakagawa T, Michishita M, Egusa AS, Sasaki T, Watanabe M, Omi T.
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Journal Title
Oncol Rep
Volume: 40
Pages: 488-494
DOI
NAID
Related Report
Peer Reviewed / Open Access
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