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Elucidation of the Mechanism of Transcription Factor OCT1 in Acquiring Therapeutic Resistance in Advanced Prostate Cancer

Research Project

Project/Area Number 19H03793
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionNihon University

Principal Investigator

OBINATA Daisuke  日本大学, 医学部, 准教授 (20624886)

Co-Investigator(Kenkyū-buntansha) 井上 聡  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (40251251)
高橋 悟  日本大学, 医学部, 教授 (50197141)
高山 賢一  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 専門副部長 (50508075)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
Fiscal Year 2021: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Keywords前立腺癌 / アンドロゲン受容体 / 転写因子 / OCT1 / 新規OCT1標的遺伝子 / アンドロゲンレセプター / PDX
Outline of Research at the Start

私たちはこれまでの一連の研究で、前立腺がん進行の中核をなすアンドロゲン受容体(AR)シグナル経路に重点をおき、1)転写協調因子OCT1によるAR協調作用と進行への関与、2)新規AR標的遺伝子群による前立腺癌増殖促進作用、ならびに3)前立腺がん細胞増殖抑制効果のある中分子ポリアミド製剤の開発を世界に先駆けて報告している。
本研究はこれら研究をさらに発展させ、患者由来多剤耐性前立腺がん培養システムを駆使して進行性前立腺がんにおける転写協調因子OCT1を中心としたARシグナル経路を探求し治療抵抗性獲得機序を解明する。

Outline of Final Research Achievements

To elucidate the mechanism of OCT1, a transcriptional regulator that influences the androgen receptor (AR) signaling pathway, we investigated the role of OCT1 in the progression of prostate cancer using homogenous prostate cancer cell lines. In addition, two patient derived xenografts established from multi-drug resistant, advanced prostate cancer (AR-positive and AR-resistant) were used in this study. Gene coverage analysis was performed to identify OCT1 target genes expressed, and several OCT1 target genes were found to be important for prostate cancer progression.

Academic Significance and Societal Importance of the Research Achievements

前立腺がんはアンドロゲンが枯渇した環境下においても、アンドロゲン受容体とそれを標的遺伝子領域に誘導する転写因子を活用し、積極的に染色体や代謝経路を変異活性化させることで、低アンドロゲン状態での生存能力を獲得していることがこれまでの研究で判明している。今回転写因子OCT1がアンドロゲン受容体が存在しない前立腺癌で単独でアンドロゲン応答遺伝子を発現させ、さらに細胞の形質をより未分化なものへ転化させる遺伝子発現を促進させていることを見出した。同意電子群を標的とすることで前立腺癌の悪性化を防止できる可能性が示唆された。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (15 results)

All 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results)

  • [Int'l Joint Research] Monash University(オーストラリア)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Monash University(オーストラリア)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Post-transcriptional Gene Regulation by MicroRNA-194 Promotes Neuroendocrine Transdifferentiation in Prostate Cancer.2021

    • Author(s)
      Fernandes RC, Toubia J, Townley S, Hanson AR, Dredge BK, Pillman KA, Bert AG, Winter JM, Iggo R, Das R, Obinata D; MURAL investigators, Sandhu S, Risbridger GP, Taylor RA, Lawrence MG, Butler LM, Zoubeidi A, Gregory PA, Tilley WD, Hickey TE, Goodall GJ, Selth LA
    • Journal Title

      Cell Rep

      Volume: 5 Issue: 1 Pages: 108585-108585

    • DOI

      10.1016/j.celrep.2020.108585

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recent Discoveries in the Androgen Receptor Pathway in Castration-Resistant Prostate Cancer2020

    • Author(s)
      Obinata Daisuke、Lawrence Mitchell G.、Takayama Kenichi、Choo Nicholas、Risbridger Gail P.、Takahashi Satoru、Inoue Satoshi
    • Journal Title

      Frontiers in Oncology

      Volume: 10 Pages: 581515-581515

    • DOI

      10.3389/fonc.2020.581515

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Preoperative CT volumetry of estimated residual kidney for prediction of postoperative chronic kidney disease in patients with renal cell carcinoma2020

    • Author(s)
      Hori Yutaro、Obinata Daisuke、Funakoshi Daigo、Sakurai Fuminori、Yoshizawa Tsuyoshi、Matsui Tsuyoshi、Mochida Junichi、Yamaguchi Kenya、Takahashi Satoru
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 25 Issue: 3 Pages: 315-321

    • DOI

      10.1007/s10157-020-01984-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful lymphatic embolization using N-butyl-2-cyanoacrylate for postoperative lymphorrhea in a patient with renal pelvic cancer2020

    • Author(s)
      Irie Yuki、Obinata Daisuke、Tsukada Jitsuro、Arakawa Shigeyuki、Kadotani Masaya、Hori Yutaro、Yoshizawa Tsuyoshi、Mochida Junichi、Yamaguchi Kenya、Takahashi Satoru
    • Journal Title

      Radiology Case Reports

      Volume: 15 Issue: 11 Pages: 2139-2143

    • DOI

      10.1016/j.radcr.2020.08.051

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low reduction of prostate volume is a significant predictor of prostate cancer at subsequent biopsy in patients with dutasteride: A retrospective study.2020

    • Author(s)
      Obinata D, Suzuki S, Yamanaka Y, Yoshizawa T, Mochida J, Yamaguchi K, Takahashi S.
    • Journal Title

      Andrologia

      Volume: 52 Issue: 11 Pages: 13810-13810

    • DOI

      10.1111/and.13810

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Epigenetic regulation of OCT1 in castration resistant prostate cancer cells2021

    • Author(s)
      Obinata D
    • Organizer
      11th Eurasian Uro-Oncology Congress
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Identification of OCT1 target genes involved in progression of castration-resistant AR-null prostate cancer2021

    • Author(s)
      Obinata D, Takayama KI, Funakoshi D, Lawrence M, Taylor R, Sandhu S, Risbridger G, Inoue S
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 治療抵抗性メカニズムから見た転移性前立腺癌治療Update2021

    • Author(s)
      大日方大亮
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 去勢抵抗性前立腺癌に関与するアンドロゲン受容体転写協調因子2021

    • Author(s)
      大日方大亮, Lawrence Mitchell, 高山賢一, 高橋悟, 井上聡
    • Organizer
      第36回前立腺シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 多剤耐性去勢抵抗性前立腺癌におけるオクタマー転写因子(OCT1)による発現調節機構の検討2021

    • Author(s)
      大日方大亮, 高山賢一, Mitchell Lawrence, Renea Taylor,Shahneen Sandhu, 船越大吾, 藤原恭子, Gail Risbridger, 高橋悟, 井上聡
    • Organizer
      第109回日本泌尿器科学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 患者由来多剤耐性去勢抵抗性前立腺癌細胞におけるOCT1の役割2020

    • Author(s)
      大日方大亮, 高山賢一, 鈴木穣, Lawrence Mitchell, Taylor Renea, Sandhu Shahneen, Risbridger Gail, 高橋悟, 井上聡
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 多剤耐性去勢抵抗性前立腺癌に対するAR転写強調因子(OCT1)標的薬剤の有効性検討2020

    • Author(s)
      大日方大亮, Mitchell Lawrence, Renea Taylor, Shahneen Sandhu, 藤原恭子, 高山賢一, 井上聡, 高橋悟, Gail Risbridger
    • Organizer
      第108回日本泌尿器科学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Recent Discoveries in the Androgen Receptor Pathway in Prostate cancer2020

    • Author(s)
      Obinata D
    • Organizer
      18th International Prostate Forum
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2019-04-18   Modified: 2023-01-30  

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