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Identification and functional analysis of telomerase suppressor genes in pancreatic cancer using chromosome engineering

Research Project

Project/Area Number 20K17688
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionTottori University

Principal Investigator

YAGYU Takuki  鳥取大学, 医学部附属病院, 医員 (00867757)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords膵がん / テロメラーゼ / 3p21.3領域 / 3p21.3 / 膵癌 / 染色体工学
Outline of Research at the Start

膵癌は、最も予後の悪い癌の一つであるが、これまでの研究で3番染色体短腕上に高頻度でヘテロ接合性喪失(LOH)が認められることが分かっている。しかし、同領域の具体的な癌抑制遺伝子の同定には至っていない。本研究では、染色体工学技術を用いてヒト正常3番染色体を膵癌細胞株に導入し、得られた細胞を次世代シークエンサーを用いて解析することにより、同領域の新規癌抑制遺伝子、特に膵癌で異常に活性が亢進しているテロメラーゼに対する抑制遺伝子の獲得を目指すものである。

Outline of Final Research Achievements

Pancreatic cancer has an approximately 10% five-year survival rate, which is a remarkably poor prognosis compared to other cancers, and the development of new therapeutic targets is an urgent issue. Telomerase, on the other hand, has little function in normal cells, but is commonly activated in many carcinomas, thus attracting attention as a molecular target.
In this study, through an experimental transfection of normal human chromosome 3 into a pancreatic cancer cell line, it was clarified that the telomerase suppressor gene is located in the 3p21.3 region in pancreatic cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究は、膵がんにおいて3番染色体短腕の特定の領域にテロメラーゼ抑制遺伝子(群)が存在することを明らかにした。またその機序は、テロメラーゼ活性中心のTERTのプロモーター活性を抑制することによる可能性が示唆された。この結果により、膵がんの新たな治療ターゲット開発の糸口となることや、膵がん発生メカニズムの理解が進むことが期待される。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (6 results)

All 2021 2020

All Journal Article (4 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Human chromosome 3p21.3 carries TERT transcriptional regulators in pancreatic cancer.2021

    • Author(s)
      Yagyu T, Ohira T, Shimizu R, Morimoto M, Murakami Y, Hanaki T, Kihara K, Matsunaga T, Yamamoto M, Tokuyasu N, Sakamoto T, Fujiwara Y, Kugoh H.
    • Journal Title

      Scientific Reports

      Volume: 28;11(1):15355. Issue: 1 Pages: 15355-15355

    • DOI

      10.1038/s41598-021-94711-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decreased mean platelet volume predicts poor prognosis in patients with pancreatic cancer2021

    • Author(s)
      Yagyu Takuki、Saito Hiroaki、Sakamoto Teruhisa、Uchinaka Ei、Morimoto Masaki、Hanaki Takehiko、Watanabe Joji、Matsunaga Tomoyuki、Yamamoto Manabu、Tokuyasu Naruo、Honjo Soichiro、Fujiwara Yoshiyuki
    • Journal Title

      BMC Surgery

      Volume: 21 Issue: 1 Pages: 8-8

    • DOI

      10.1186/s12893-020-00976-5

    • Related Report
      2020 Research-status Report
  • [Journal Article] Sarcopenia as a prognostic factor in patients with recurrent pancreatic cancer: a retrospective study2020

    • Author(s)
      Sakamoto Teruhisa、Yagyu Takuki、Uchinaka Ei、Miyatani Kozo、Hanaki Takehiko、Kihara Kyoichi、Matsunaga Tomoyuki、Yamamoto Manabu、Tokuyasu Naruo、Honjo Soichiro、Fujiwara Yoshiyuki
    • Journal Title

      World Journal of Surgical Oncology

      Volume: 18 Issue: 1 Pages: 221-221

    • DOI

      10.1186/s12957-020-01981-x

    • Related Report
      2020 Research-status Report
  • [Journal Article] Combined prognostic nutritional index ratio and serum amylase level during the early postoperative period predicts pancreatic fistula following pancreaticoduodenectomy2020

    • Author(s)
      Sakamoto Teruhisa、Yagyu Takuki、Uchinaka Ei、Morimoto Masaki、Hanaki Takehiko、Watanabe Joji、Yamamoto Manabu、Matsunaga Tomoyuki、Tokuyasu Naruo、Honjo Soichiro、Fujiwara Yoshiyuki
    • Journal Title

      BMC Surgery

      Volume: 20 Issue: 1 Pages: 178-178

    • DOI

      10.1186/s12893-020-00838-0

    • Related Report
      2020 Research-status Report
  • [Presentation] 染色体工学技術を応用した膵がんにおけるテロメラーゼ抑制領域3p21.3の同定2021

    • Author(s)
      柳生拓輝、大平崇人、花木武彦、木原恭一、松永知之、山本学、徳安成郎、坂本照尚、久郷裕之、藤原義之
    • Organizer
      第76回日本消化器外科学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Identification of a telomerase repressor region on 3p21.3 by chromosome engineering2021

    • Author(s)
      柳生拓輝、大平崇人、清水龍太郎、藤原義之、久郷裕之
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report

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Published: 2020-04-28   Modified: 2023-01-30  

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