Development of diagnostic and therapeutic strategies for hormone therapy-resistant prostate cancer diagnosis and treatment using the canine AR complex as a origin.
Project/Area Number |
19K06390
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 42020:Veterinary medical science-related
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Research Institution | Nippon Veterinary and Life Science University |
Principal Investigator |
Ochiai Kazuhiko 日本獣医生命科学大学, 獣医学部, 准教授 (30550488)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | イヌ / 前立腺がん / アンドロゲン受容体 / SGTA / REIC/Dkk-3 / REIC/Dkk3 / AR signaling |
Outline of Research at the Start |
本申請課題においては、ヒトで問題となっているホルモン療法抵抗性前立腺がんと若年期での去勢というイヌ独特なライフスタイルによって生じるホルモン療法難治性イヌ前立腺がんの病態近似に着目する。去勢イヌで前立腺がん発症機構が解明できればヒト前立腺がんがホルモン療法抵抗性を獲得する機構の解明に繋がると考え、前立腺がん発症起点となるアンドロゲン受容体(AR)の成熟機構に関わる因子を中心に生化学・細胞生物学的手法を用いて精査する。
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Outline of Final Research Achievements |
Androgen receptor signaling (AR signaling)-independent prostate, which is refractory in humans, approximates canine hormone therapy-resistant prostate cancer pathology that occurs under castration conditions, and is of great significance in elucidating the mechanisms underlying the development and refractoriness of canine prostate cancer. In order to elucidate the mechanism of canine AR signaling under androgen-independent conditions, the applicant has cloned the entire length of the canine AR and used it in various experiments. In this context, the effect of the number of glutamine (Q) repeats present in the canine AR on the AR signaling mechanism was examined from a cell biological perspective. The role of REIC/Dkk-2 and SGTA as regulators of this mechanism was also examined.
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Academic Significance and Societal Importance of the Research Achievements |
イヌは去勢により雄性ホルモン分泌の遮断を行うにもかかわらず、雄性ホルモン誘導性の前立腺がんを発症する。このメカニズム解明はヒト前立腺がんのうち、ホルモン療法に抵抗性を示す難治性症例の病態解明に繋がることが期待される。本申請課題では、イヌのアンドロゲン受容体がもつ構造多型がアンドロゲン受容体シグナル伝達におよぼす影響について解析した。また、本機構に対する、がん抑制遺伝子REIC/Dkk-3およびコシャペロン分子であるSGTA分子の関与についても解析した。
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Report
(4 results)
Research Products
(22 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
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Peer Reviewed / Open Access
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[Journal Article] Involvement of Nestin in the Progression of Canine Mammary Carcinoma.2021
Author(s)
Yoshimura H, Moriya M, Yoshida A, Yamamoto M, Machida Y, Ochiai K, Michishita M, Nakagawa T, Matsuda Y, Takahashi K, Kamiya S, Ishiwata T
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Journal Title
Vet Pathol.
Volume: 58
Issue: 5
Pages: 994-1003
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Novel canine isocitrate dehydrogenase 1 mutation Y208C attenuates dimerization ability2020
Author(s)
Kawakami S, Michishita M, Sakaue M, Morimatsu M, Uemura M, Kashiwagi N, Maeda M, Machida Y, Azakami D, Egusa AS, Onozawa E, Ishioka K, Watanabe M, Tanaka Y, Omi T, Ochiai K.
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Journal Title
Oncology Letters
Volume: 20
Issue: 6
Pages: 351-351
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Dkk3/REIC, an N-glycosylated Protein, Is a Physiological Endoplasmic Reticulum Stress Inducer in the Mouse Adrenal Gland2020
Author(s)
Fujita, H., Bando, T., Oyadomari, S., Ochiai, K., Watanabe, M., Kumon, H. & Ohuchi, H.
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Journal Title
Acta Medica Okayama
Volume: 74
Issue: 3
Pages: 199-208
DOI
NAID
URL
Related Report
Peer Reviewed / Open Access
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[Journal Article] Metabolite profiling in sphere-forming cells from canine mammary adenocarcinoma cell lines using gas chromatography-mass spectrometry2019
Author(s)
Michishita M, Saito N, Nozawa S, Furumoto R, Nakagawa T, Sato T, Ochiai K, Azakami D, Katayama K, Nakahira R, Tazaki H, Machida Y, Ishiwata T.
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Journal Title
Journal of Veterinary Medical Science
Volume: 81
Issue: 9
Pages: 1238-1248
DOI
NAID
ISSN
0916-7250, 1347-7439
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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[Presentation] 市販GS製剤による猫コロナウイルス増殖抑制効果の検討2020
Author(s)
田中 良和, 林田 真琴, 落合 和彦, 前田 まりか, 廣瀬 紗千, 田辺 愛理, 野中 柚希, 久保田 匠, 豊島 麻美子, 大矢 真里奈, 川越 美琴, 薩見 春輝, 石川 創
Organizer
第163回日本獣医学会学術集会
Related Report
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