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Elucidation of the signaling pathways that induce gene amplification

Research Project

Project/Area Number 18K19281
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
Research InstitutionTohoku University

Principal Investigator

NAKAYAMA Keiko  東北大学, 医学系研究科, 教授 (60294972)

Co-Investigator(Kenkyū-buntansha) 城田 松之  東北大学, 医学系研究科, 講師 (00549462)
舟山 亮  東北大学, 医学系研究科, 助教 (20452295)
中川 直  東北大学, 医学系研究科, 助教 (30707013)
Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords遺伝子増幅 / TGF-β刺激 / Myc遺伝子 / シグナル伝達経路
Outline of Final Research Achievements

When the time course of amplification after TGF-β stimulation was examined, cell proliferation had already stopped on the second day after the start of stimulation, but no gene amplification was observed, and amplification occurred on the 28th day.
To confirm that this is a universal phenomenon in NMuMG cells, we purchased new NMuMG cells and further cloned the cells by limitting dilution. After stimulation with TGF-β, all the clones stopped growing and then started growing again, avoiding the inhibition of growth by TGF-β, as previously reported. However, no amplification of myc was observed in these clones, suggesting that this is not a universal phenomenon in NMuMG cells.

Academic Significance and Societal Importance of the Research Achievements

がん・悪性新生物は、長く我が国の死亡原因の第一位であり、その克服は喫緊の課題である。次世代シークエンサーを活用した新しい測定技術によりがんの多くの細胞は遺伝子の数の異常があることが、知られるようになったが、その分子機構は不明である。本研究ではそれを明らかにする新しいモデルの確立を目指したが、現在のところ普遍的なモデルとしての確立には至らなかった。この問題は生物学的としても悪性新生物を理解する上でも興味深い課題であり、今後も研究を進めて行くことが重要である。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (23 results)

All 2021 2020 2019 2018 Other

All Journal Article (15 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 15 results,  Open Access: 10 results) Presentation (6 results) Remarks (2 results)

  • [Journal Article] Study Profile of the Tohoku Medical Megabank Community-Based Cohort Study2021

    • Author(s)
      Hozawa A, Tanno K, Nakaya N, Nakamura T, Tsuchiya N, Hirata T, Narita A, Kogure M, Nochioka K, Sasaki R, Takanashi N, Otsuka K, Sakata K, Kuriyama S, Kikuya M, 13名略, Kobayashi T, 53名略, Yamamoto M.
    • Journal Title

      Journal of Epidemiology

      Volume: 31 Issue: 1 Pages: 65-76

    • DOI

      10.2188/jea.JE20190271

    • NAID

      130007966030

    • ISSN
      0917-5040, 1349-9092
    • Year and Date
      2021-01-05
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metabolic and pathologic profiles of human LSS deficiency recapitulated in mice2020

    • Author(s)
      Wada Yoichi、Kikuchi Atsuo、Kaga Akimune、Shimizu Naoki、Ito Junya、Onuma Ryo、Fujishima Fumiyoshi、Totsune Eriko、Sato Ryo、Niihori Tetsuya、Shirota Matsuyuki、Funayama Ryo、Sato Kota、Nakazawa Toru、Nakayama Keiko、Aoki Yoko、Aiba Setsuya、Nakagawa Kiyotaka、Kure Shigeo
    • Journal Title

      PLOS Genetics

      Volume: 16 Issue: 2 Pages: e1008628-e1008628

    • DOI

      10.1371/journal.pgen.1008628

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Variants That Affect Function of Calcium Channel TRPV6 Are Associated With Early-Onset Chronic Pancreatitis.2020

    • Author(s)
      Masamune A, Kotani H, Sorgel FL, Chen JM, Hamada S, Sakaguchi R, Masson E, Nakano E, et al.
    • Journal Title

      Gastroenterology

      Volume: - Issue: 6 Pages: 1626-1641

    • DOI

      10.1053/j.gastro.2020.01.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] BACH1 Promotes Pancreatic Cancer Metastasis by Repressing Epithelial Genes and Enhancing Epithelial-Mesenchymal Transition2020

    • Author(s)
      Sato Masaki、Matsumoto Mitsuyo、Saiki Yuriko、Alam Mahabub、Nishizawa Hironari、Rokugo Masahiro、Brydun Andrey、Yamada Shinji、Kaneko Mika K.、Funayama Ryo、Ito Mamoru、Kato Yukinari、Nakayama Keiko、Unno Michiaki、Igarashi Kazuhiko
    • Journal Title

      Cancer Research

      Volume: 80 Issue: 6 Pages: 1279-1292

    • DOI

      10.1158/0008-5472.can-18-4099

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Knockout Mouse Models Provide Insight into the Biological Functions of CRL1 Components.2020

    • Author(s)
      Nakagawa T, Nakayama K, Nakayama KI.
    • Journal Title

      Adv Exp Med Biol.

      Volume: 1217 Pages: 147-171

    • DOI

      10.1007/978-981-15-1025-0_10

    • ISBN
      9789811510243, 9789811510250
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cohort Profile: Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study): rationale, progress and perspective.2020

    • Author(s)
      Kuriyama S, Metoki H, Kikuya M, Obara T, Ishikuro M, Yamanaka C, Nagai M, Matsubara H, Kobayashi T, 57名略, Yamamoto M.
    • Journal Title

      Int J Epidemiol.

      Volume: 49(1) Issue: 1 Pages: 18-19

    • DOI

      10.1093/ije/dyz169

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biallelic variants/mutations of IL1RAP in patients with steroid-sensitive nephrotic syndrome2019

    • Author(s)
      Niitsuma Sou、Kudo Hiroki、Kikuchi Atsuo、Hayashi Takaya、Kumakura Satoshi、Kobayashi Shuhei、Okuyama Yuko、Kumagai Naonori、Niihori Tetsuya、Aoki Yoko、So Takanori、Funayama Ryo、Nakayama Keiko、Shirota Matsuyuki、Kondo Shuji、Kagami Shoji、Tsukaguchi Hiroyasu、Iijima Kazumoto、Kure Shigeo、Ishii Naoto
    • Journal Title

      International Immunology

      Volume: 32 Issue: 4 Pages: 283-292

    • DOI

      10.1093/intimm/dxz081

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathogenic mutations in the ALS gene CCNF cause cytoplasmic mislocalization of Cyclin F and elevated VCP ATPase activity.2019

    • Author(s)
      Yu Y, Nakagawa T, Morohoshi A, Nakagawa M, Ishida N, Suzuki N, Aoki M, Nakayama K.
    • Journal Title

      Hum Mol Genet

      Volume: 28 Issue: 20 Pages: 3486-3497

    • DOI

      10.1093/hmg/ddz119

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of NRAS mutation in cell-free DNA biological fluids from patients with kaposiform lymphangiomatosis2019

    • Author(s)
      Ozeki Michio、Aoki Yoko、Nozawa Akifumi、Yasue Shiho、Endo Saori、Hori Yumiko、Matsuoka Kentaro、Niihori Tetsuya、Funayama Ryo、Shirota Matsuyuki、Nakayama Keiko、Fukao Toshiyuki
    • Journal Title

      Orphanet Journal of Rare Diseases

      Volume: 14 Issue: 1 Pages: 215-215

    • DOI

      10.1186/s13023-019-1191-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cancer‐associated fibroblasts secrete Wnt2 to promote cancer progression in colorectal cancer2019

    • Author(s)
      Aizawa Takashi、Karasawa Hideaki、Funayama Ryo、Shirota Matsuyuki、Suzuki Takashi、Maeda Shimpei、Suzuki Hideyuki、Yamamura Akihiro、Naitoh Takeshi、Nakayama Keiko、Unno Michiaki
    • Journal Title

      Cancer Medicine

      Volume: 8 Issue: 14 Pages: 6370-6382

    • DOI

      10.1002/cam4.2523

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aberrant axon branching via Fos-B dysregulation in FUS-ALS motor neurons.2019

    • Author(s)
      Akiyama T, Suzuki N, Ishikawa M, Fujimori K, Sone T, Kawada J, Funayama R, Fujishima F, Mitsuzawa S, Ikeda K, Ono H, Shijo T, Osana S, Shirota M, Nakagawa T, et al.
    • Journal Title

      EBioMedicine

      Volume: 45 Pages: 362-378

    • DOI

      10.1016/j.ebiom.2019.06.013

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Germline-Activating RRAS2 Mutations Cause Noonan Syndrome2019

    • Author(s)
      Niihori Tetsuya、Nagai Koki、Fujita Atsushi、Ohashi Hirofumi、Okamoto Nobuhiko、Okada Satoshi、Harada Atsuko、Kihara Hirotaka、Arbogast Thomas、Funayama Ryo、Shirota Matsuyuki、Nakayama Keiko、Abe Taiki、Inoue Shin-ichi、Tsai I-Chun、Matsumoto Naomichi、Davis Erica E.、Katsanis Nicholas、Aoki Yoko
    • Journal Title

      The American Journal of Human Genetics

      Volume: 104 Issue: 6 Pages: 1233-1240

    • DOI

      10.1016/j.ajhg.2019.04.014

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recurrent de novo MAPK8IP3 variants cause neurological phenotypes2019

    • Author(s)
      Iwasawa Shinya、Yanagi Kumiko、Kikuchi Atsuo、Kobayashi Yasuko、Haginoya Kazuhiro、Matsumoto Hiroshi、Kurosawa Kenji、Ochiai Masayuki、Sakai Yasunari、Fujita Atsushi、Miyake Noriko、Niihori Tetsuya、ら
    • Journal Title

      Annals of Neurology

      Volume: - Issue: 6 Pages: 927-933

    • DOI

      10.1002/ana.25481

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] The ubiquitin ligase subunit β-TrCP in Sertoli cells is essential for spermatogenesis in mice.2019

    • Author(s)
      Morohoshi, A., Nakagawa, T., Nakano, S., Nagasawa, Y., Nakayama, K.
    • Journal Title

      Dev Biol.

      Volume: 445 Issue: 2 Pages: 178-188

    • DOI

      10.1016/j.ydbio.2018.10.023

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Peroxisome biogenesis deficiency attenuates the BDNF-TrkB pathway-mediated development of the cerebellum2018

    • Author(s)
      Abe Yuichi、Honsho Masanori、Itoh Ryota、Kawaguchi Ryoko、Fujitani Masashi、Fujiwara Kazushirou、Hirokane Masaaki、Matsuzaki Takashi、Nakayama Keiko、Ohgi Ryohei、Marutani Toshihiro、Nakayama Keiichi I、Yamashita Toshihide、Fujiki Yukio
    • Journal Title

      Life Science Alliance

      Volume: 1 Issue: 6 Pages: 1-17

    • DOI

      10.26508/lsa.201800062

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 蛋白分解異常による新規筋萎縮性側索硬化症の発症機構2019

    • Author(s)
      渡辺 靖章, 中川 直, 鈴木 直輝, 割田 仁, 中山 啓子, 青木 正志
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 知的障害・自閉症関連因子SETD5によるrDNAのエピジェネティック制御2019

    • Author(s)
      中川 直, 中山 啓子
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Alternative Splicing of FBLN2 generates two proteins with different N-linked glycosylation patterns2019

    • Author(s)
      Wei Chen Kao,Ryo Funayama, Keiko Nakayama
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ユビキチン化によるFACT複合体の機能制御2018

    • Author(s)
      中川直、諸星茜、中山啓子
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 大腸がんにおけるFibulin2スプライスバリアントの役割2018

    • Author(s)
      舟山亮、遠山慎吾、高唯真、中山啓子
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Mutation of cyclin F may contribute to Amyotrophic Lateral Sclerosis pathogensis by affecting VCP ATPase activity2018

    • Author(s)
      Yujao Yu, Akane Morohoshi, Tadashi Nakagawa, Keiko Nakayama
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Remarks] 東北大学大学院医学系研究科附属創生応用医学研究センターがん医学コアセンター細胞増殖制御分野

    • URL

      http://www.devgen.med.tohoku.ac.jp/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 東北大学医学系研究科細胞装飾制御分野HP

    • URL

      http://www.devgen.med.tohoku.ac.jp/

    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2021-02-19  

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