Development of immunotherapy for castration resistant prostate cancer targeting a novel cofactor of RORgamma
| Project/Area Number |
18K09162
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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 | The University of Tokyo (2020-2022)
Teikyo University (2018-2019) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小林 隆志 大分大学, 医学部, 教授 (30380520)
中川 徹 帝京大学, 医学部, 教授 (40591730)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 前立腺癌 / RORγ / ESS2 / ＲＯＲγ / ＥＳＳ２ / 免疫療法 |
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| Outline of Final Research Achievements |
We screened ESS2 gene as a novel cofactor of ROR gamma. We evaluated the involvement of the transcriptional coregulator ESS2 in prostate cancer. ESS2-knockdown PC3 cells dramatically inhibited proliferation in tumor xenografts in nude mice. Microarray analysis revealed that ESS2 regulated mRNA levels of chromodomain helicase DNA binding protein 1 (CHD1)-related genes and other cancer-related genes, such as PPAR-γ, WNT5A, and
TGF-Β, in prostate cancer. ESS2 knockdown reduced nuclear factor (NF)-κB/CHD1 recruitment and histone H3K36me3 levels on the promoters of target genes (TNF and CCL2). Tamoxifen-inducible Ess2-knockout mice showed delayed prostate development with hypoplasia and disruption of luminal cells in the ventral prostate.
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| Academic Significance and Societal Importance of the Research Achievements |
去勢抵抗性前立腺癌（CRPC)に対して種々の治療薬が臨床応用されているもののCRPCに至り死亡する症例数は本邦でも年間12,000例と多く、治療成績の改善には副作用の少ない新規治療薬の開発が望まれる。今回我々が同定した新規ESS2遺伝子は前立腺癌症例の9割以上に高発現していることが分かり治療ターゲットとして適切である。機能解析によりESS2遺伝子が前立腺癌増殖に強く作用することが証明された。また作用機序として細胞のクロマチンリモデリング因子に作用し増殖を制御することが分かった。このESS2を阻害する薬剤が前立腺癌の新規治療薬として治療成績の改善に繋がると考えられる。
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Report
(6 results)
Research Products
(12 results)
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[Journal Article] Transcriptional coregulator Ess2 controls survival of post-thymic CD4+ T cells through the Myc and IL-7 signaling pathways2022
Author(s)
Takada I‡, Hidano S‡, Takahashi S‡, Ogawa H, Tsuchiya M, Yokoyama A, Sato S, Ochi H, Nakagawa T, Kobayashi T, Nakagawa S, Makishima M
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Journal Title
Journal of Biological Chemistry
Volume: 298
Pages: 102342-102342
Related Report
Peer Reviewed / Open Access
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