Study on novel mechanism of breast cancer development by modulation of mitochondrial control
| Project/Area Number |
18K19473
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 50:Oncology and related fields
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Miki Yoshio 東京医科歯科大学, 難治疾患研究所, 教授 (10281594)
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| Co-Investigator(Kenkyū-buntansha) |
砂田 成章 東京医科歯科大学, 難治疾患研究所, 助教 (70807677)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | ミトコンドリア / マイトファジー / BRCA1, BRCA2 / Mfn / BRCA1/2 / 乳がん / オートファジー |
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| Outline of Final Research Achievements |
A group of molecules including BRCA1 and BRCA2 was reported to function in the mitophagy pathway. Therefore, we analyzed a novel mechanism of breast cancer development by modulation of mitochondrial control. First, we discovered the interaction between BRCA2 and Mfn present in the outer mitochondrial membrane. Mfn drives fusion of mitochondria in mitochondrial dynamics. Next, we constructed a system for observing intracellular fusion of mitochondria and analyzed the effects of BRCA2 expression and suppression on the fusion function. Furthermore, we have determined the functional domain in BRCA2 that binds to Mfn and regulates the mitochondrial function. We have introduced a breast cancer inducing BRCA2 mutation in the region and are analyzing the modulation of mitochondrial regulation.
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| Academic Significance and Societal Importance of the Research Achievements |
ミトコンドリア制御機構におけるBRCA2 の機能解明は、新しい乳がん発症機構の発見に加え、新規治療ターゲットの提案という医学的にも社会的にも要求度の高い成果につながると期待される。
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Report
(3 results)
Research Products
(20 results)
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[Journal Article] Non-V600E BRAF mutations and EGFR signaling pathway in colorectal cancer.2019
Author(s)
Osumi H, Shinozaki E, Wakatsuki T, Suenaga M, Ichimura T, Ogura M, Takahari D, Ooki A, Suzuki T, Ota Y, Nakayama I, Chin K, Miki Y, Yamaguchi K.
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Journal Title
Int J Cancer.
Volume: 145
Issue: 9
Pages: 2488-2495
DOI
Related Report
Peer Reviewed
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[Journal Article] Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.2019
Author(s)
Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, Katagiri T, Yoshida T, Nakamura S, Sugano K, Miki Y, Hirata M, Matsuda K, Spurdle AB, Kubo M.
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Journal Title
Nat Commun.
Volume: 9
Issue: 1
Pages: 4083-4083
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Phase II trial of biweekly cetuximab and irinotecan as third-line therapy for pretreated KRAS exon 2 wild-type colorectal cancer.2018
Author(s)
Osumi H, Shinozaki E, Mashima T, Wakatsuki T, Suenaga M, Ichimura T, Ogura M, Ota Y, Nakayama I, Takahari D, Chin K, Miki Y, Yamaguchi K
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Journal Title
Cancer Sci.
Volume: 109
Issue: 8
Pages: 2567-2575
DOI
Related Report
Peer Reviewed / Open Access
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