exploring innovative therapeutic target for bone metastatic prostate cancer based on analysis of molecular mechanism.
| Project/Area Number |
18K09168
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | Ehime University |
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Principal Investigator |
SAIKA TAKASHI 愛媛大学, 医学系研究科, 教授 (10314676)
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| Co-Investigator(Kenkyū-buntansha) |
今井 祐記 愛媛大学, プロテオサイエンスセンター, 教授 (10423873)
菊川 忠彦 愛媛大学, 医学系研究科, 准教授 (70444734)
三浦 徳宣 愛媛大学, 医学部附属病院, 講師 (80554427)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 前立腺癌 / 骨転移 / 前立腺がん / 転移制御 / 分子機構 / データベース |
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| Outline of Final Research Achievements |
The prognosis of patients with progressive prostate cancers that are hormone refractory and/or have bone metastasis is poor. we identified G Protein-Coupled Receptor Class C Group 5 Member A (GPRC5A) as a candidate therapeutic molecule using integrative gene expression analyses of registered data sets for prostate cancer cell lines. Kaplan Meier analysis of TCGA data sets revealed that patients who have high GPRC5A expression had significantly shorter overall survival. PC3 prostate cancer cells with CRISPR/Cas9-mediated GPRC5A knockout exhibited significantly reduced cell proliferation both in vitro and in vivo. RNA-seq revealed that GPRC5A KO PC3 cells had dysregulated expression of cell cycle-related genes, leading to cell cycle arrest at the G2/M phase. Furthermore, GPRC5A KO PC3 cells failed to establish bone metastasis in xenograft mice models. Our findings indicate that GPRC5A can be a possible therapeutic target and prognostic marker molecule for progressive prostate cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果により、前立腺癌進展の病態の解明と新規治療方法および骨転移の予防や骨転移発生の予測の治療基盤の構築が進むと期待できる。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] GPRC5A facilitates cell proliferation through cell cycle regulation and correlates with bone metastasis in prostate cancer2020
Author(s)
Sawada Y, Kikugawa T, Iio H, Sakakibara I, Yoshida S, Ikedo A, Yanagihara Y, Saeki N, Gyorffy B, Kishida T, Okubo Y, Nakamura Y, Miyagi Y, Saika T, Imai Y.
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Journal Title
International Journal of Cancer
Volume: 146
Issue: 5
Pages: 1369-1382
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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