Drug development and biological function study of novel estrogen receptor activity modulator BIG3 protein
| Project/Area Number |
25293079
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KATAGIRI Toyomasa 徳島大学, 疾患プロテオゲノム研究センター, 教授 (60291895)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUGUCHI Kenji 国立研究開発法人医薬基盤, 健康・栄養研究所・医薬基盤研究所 バイオインフォマティクスプロジェクト, プロジェクトリーダー (50450896)
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| Co-Investigator(Renkei-kenkyūsha) |
YOSHIMARU Tetsuro 徳島大学, 疾患プロテオゲノム研究センター, 講師 (80424729)
MIYOSHI Yasuo 兵庫医科大学, 医学部, 教授 (50283784)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2013: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | 癌 / ゲノム / 蛋白質 / ホルモン / 乳癌 / エストロゲン / システムバイオロジー / ホルモン療法耐性 / ゲノム創薬 |
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| Outline of Final Research Achievements |
In this study, we identified that Xanthohumol a natural compound effectively inhibits the BIG3(former name; ERAP1)-PHB2 interaction, resulting in suppression of estrogen (E2)-dependent tumor growth of breast cancer in vitro and in vivo. In addition, we discovered that the mechanism by which BIG3 blocks the nuclear translocation of PHB2 via interactions with KPNA1, 5, and 6, in estrogen receptor (ER) α-positive breast cancer cells. Moreover, we further demonstrated that BIG3 interacts serine/threonine protein phosphatase and dephosphorylates the E2-dependent phosphorylation of PHB2 in breast cancer cells. These findings can provide therapeutic strategies for controlling E2/ERα signals in breast cancer cells.
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Activation of mTOR/S6K But Not MAPK Pathways Might Be Associated With High Ki-67, ER+, and HER2- Breast Cancer.2014
Author(s)
Yanai A, Inoue N, Yagi T, Nishimukai A, Miyagawa Y, Murase K, Imamura M, Enomoto Y, Takatsuka Y, Watanabe T, Hirota S, Sasa M, Katagiri T, Miyoshi Y.
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Journal Title
Clinical Breast Cancer
Volume: -
Issue: 3
Pages: 197-203
DOI
Related Report
Peer Reviewed
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[Journal Article] Targeting BIG3-PHB2 interaction to overcome tamoxifen resistance in breast cancer cells2013
Author(s)
T. Yoshimaru, M. Komatsu, T. Matsuo, Y.-A. Chen, Y. Murakami, K. Mizuguchi, E. Mizohata, T. Inoue, M. Akiyama, R. Yamaguchi, S. Imoto, S. Miyano, Y. Miyoshi, M. Sasa, Y. Nakamura, and T. Katagiri
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Journal Title
Nature Communications
Volume: 4
Issue: 1
Pages: 2433-2433
DOI
Related Report
Peer Reviewed
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