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Comprehensive functional analysis of the Meis1 pathway in the multistep carcinogenesis process

Research Project

Project/Area Number 18K07080
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionChiba Cancer Center (Research Institute)

Principal Investigator

Wakabayashi Yuichi  千葉県がんセンター(研究所), がんゲノムセンター 実験動物研究部, 部長 (40303119)

Co-Investigator(Kenkyū-buntansha) 磯貝 恵理子  千葉県がんセンター(研究所), 発がん研究グループ 実験動物研究室, 上席研究員 (40300917)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords化学はつがん / Meis1 / RNA sequencing / Chip sequencing / 化学発がん / パピローマ / 扁平上皮がん / DMBA / TPA
Outline of Final Research Achievements

Meis1 knockdown cell lines were generated using three cell lines: C5N, derived from normal skin keratinocytes, and B9 and D3, derived from squamous cell carcinoma of the skin, and RNA sequencing was performed. The results showed that high-molecular-weight Keratin5/6a/6b/14/15, which are also used as epithelial cell markers, were upregulated in the C5N and B9-Meis1 knockdown cell lines. The results of RNA sequencing were confirmed when analyzed in conjunction with the Meis1-ChIP-seq data.

Academic Significance and Societal Importance of the Research Achievements

現在、ヒトがんの大規模次世代sequenceが行われているが本課題はそれらとは一線を画し、再現性良くマウスに腫瘍を誘導することのできるマウス皮膚化学発がんモデルを中心にすえたものである。Meis1は古くから研究されているがその機能に関しては不明な点が多く治療標的とすることが困難ながん遺伝子である。その経路を解明することは新たながん治療標的の解明へとつながり、本課題の遂行は基礎科学的解明にとどまらずライフイノベーションの実現に寄与するものである。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (30 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (12 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (17 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] <i>Meis1</i> plays roles in cortical development through regulation of cellular proliferative capacity in the embryonic cerebrum2022

    • Author(s)
      ISOGAI Eriko、OKUMURA Kazuhiro、SAITO Megumi、TOKUNAGA Yurika、WAKABAYASHI Yuichi
    • Journal Title

      Biomedical Research

      Volume: 43 Issue: 3 Pages: 91-97

    • DOI

      10.2220/biomedres.43.91

    • ISSN
      0388-6107, 1880-313X
    • Year and Date
      2022-06-19
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional Polymorphism in Pak1?3′ Untranslated Region Alters Skin Tumor Susceptibility by Alternative Polyadenylation2022

    • Author(s)
      Okumura Kazuhiro、Saito Megumi、Isogai Eriko、Tokunaga Yurika、Hasegawa Yoshinori、Araki Kimi、Wakabayashi Yuichi
    • Journal Title

      Journal of Investigative Dermatology

      Volume: XXX Issue: 9 Pages: 2323-2333

    • DOI

      10.1016/j.jid.2022.02.009

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PHLDA3 Is an Important Downstream Mediator of p53 in Squamous Cell Carcinogenesis2022

    • Author(s)
      Saito Megumi、Sada Akane、Fukuyo Masaki、Aoki Kiyono、Okumura Kazuhiro、Tabata Yuko、Chen Yu、Kaneda Atsushi、Wakabayashi Yuichi、Ohki Rieko
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 142 Issue: 21 Pages: 02271-5

    • DOI

      10.1016/j.jid.2021.09.007

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Japanese Wild-Derived Inbred Mouse Strain, MSM/Ms in Cancer Research.2021

    • Author(s)
      Kazuhiro Okumura, Megumi Saito, Eriko Isogai, Yuichi Wakabayashi
    • Journal Title

      Cancers

      Volume: 13 Issue: 5 Pages: 1026-1039

    • DOI

      10.3390/cancers13051026

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A wild-derived inbred mouse strain, MSM/Ms, provides insights into novel skin tumor susceptibility genes2021

    • Author(s)
      Okumura K, Saito M, Wakabayashi Y.
    • Journal Title

      Experimental Animals

      Volume: 70 Issue: 3 Pages: 272-283

    • DOI

      10.1538/expanim.21-0017

    • NAID

      130008072157

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pak1 maintains epidermal stem cells by regulating Langerhans cells and is required for skin carcinogenesis2020

    • Author(s)
      Okumura K,Saito M, Yoshizawa Y, Ito Y, Isogai E, Araki K, Wakabayashi Y
    • Journal Title

      Oncogene

      Volume: - Issue: 24 Pages: 4756-4769

    • DOI

      10.1038/s41388-020-1323-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CENP-50 is required for papilloma development in the two-stage skin carcinogenesis model.2020

    • Author(s)
      2.Saito M, Kagawa N, Okumura K, Munakata H, Isogai E, Fukagawa T, Wakabayashi Y.
    • Journal Title

      Cancer Science.

      Volume: 111 Issue: 8 Pages: 2850-2860

    • DOI

      10.1111/cas.14533

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The role of calcium metabolism in keratinocyte differentiation.2020

    • Author(s)
      Okumura K, Wakabayashi Y.
    • Journal Title

      Trends in Cancer Research.

      Volume: 14 Pages: 45-47

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] The role of calcium metabolism in keratinocyte differentiation2020

    • Author(s)
      Okumura K, Wakabayashi Y
    • Journal Title

      Trends in Cancer Research.

      Volume: 14 Pages: 45-47

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Polymorphic Variant in p19Arf Confers Resistance to Chemically Induced Skin Tumors by Activating the p53 Pathway2019

    • Author(s)
      Saito M, Okumura K, Isogai E, Araki K, Tanikawa C, Matsuda K, Kamijo T, Kominami R, Wakabayashi Y.
    • Journal Title

      Journal of Investigative Dermatology

      Volume: in press Issue: 7 Pages: 30032-6

    • DOI

      10.1016/j.jid.2018.12.027

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Time-Series Analysis of Tumorigenesis in a Murine Skin Carcinogenesis Model2018

    • Author(s)
      Aoto Y, Okumura K, Hachiya T, Hase S, Sato K, Wakabayashi Y, Ishikawa F and Sakakibara Y.
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 12994-12994

    • DOI

      10.1038/s41598-018-31349-x

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The role of PTH in mouse skin tumorigenesis2018

    • Author(s)
      Okumura K, Saito M, and Wakabayashi Y.
    • Journal Title

      Integrative Cancer Science and Therapeutics

      Volume: 5 Issue: 2 Pages: 1000271-1000271

    • DOI

      10.15761/icst.1000271

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Pak1-3’UTRの機能的多型は選択的ポリアデニル化を介して皮膚腫瘍感受性を制御する2022

    • Author(s)
      奥村和弘、齋藤 慈, 徳永夕莉香, 磯貝恵理子, 荒木喜美, 若林雄一
    • Organizer
      第69回日本実験動物学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 樹状細胞におけるPak1欠損はDMBA/TPA多段階皮膚がんによる腫瘍形成を抑制する2022

    • Author(s)
      奥村和弘、徳永夕莉花、磯貝恵理子、荒木喜美、若林雄一
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Cenpc-cΔex2-4 promotes tumor development in DMBA/TPA skin carcinogenesis model2022

    • Author(s)
      Tokunaga Y, Okumura K, Isogai E, Hara M, Fukagawa T, Yuichi Wakabayashi Y.
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Pak1の3’UTR多型は代替ポリアデニル化を制御しマウス皮膚がん感受性に影響を与える2021

    • Author(s)
      奥村和弘、斎藤慈、磯貝恵理子、荒木喜美、若林雄一
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] MSM由来ES細胞を用いた発がん抵抗性遺伝子座の解析2021

    • Author(s)
      若林雄一
    • Organizer
      2020年度先端モデル動物プラットフォーム成果発表会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] ランゲルハンス細胞のPak1遺伝子は皮膚幹細胞の維持に関与し多段階皮膚発がんを制御する2020

    • Author(s)
      奥村和弘、斎藤慈、吉澤康博、磯貝恵理子、若林雄一
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] マウス系統間のPak1-3`UTRのSNPsは発現減少と腫瘍抑制に関連する2019

    • Author(s)
      奥村和弘、斎藤慈、磯貝恵理子、荒木 喜美、若林雄一
    • Organizer
      第66回日本実験動物学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] MSMマウスにおける腫瘍抵抗性遺伝子座の探索2019

    • Author(s)
      奥村和弘、斎藤慈、吉澤康博、磯貝恵理子、荒木 喜美、若林雄一
    • Organizer
      第32回モロシヌス研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 順遺伝学に基づくMSMマウスの発がん抵抗性の解明2019

    • Author(s)
      奥村和弘、斎藤慈、磯貝恵理子、荒木 喜美、若林雄一
    • Organizer
      第34回発癌病理研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 日本産野生由来近交系マウスMSMを用いた皮膚がん修飾因子の同定2019

    • Author(s)
      奥村和弘、斎藤慈、磯貝恵理子、若林雄一
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Meis1の大脳皮質発生への関連性の検討2019

    • Author(s)
      磯貝恵理子、奥村和弘、斎藤慈、吉澤康博、田村優希、若林雄一
    • Organizer
      第32回モロシヌス研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 順遺伝学的手法により明らかとなったマウス副甲状腺ホルモンの腫瘍抑制効果2018

    • Author(s)
      奥村和弘, 斎藤慈, 磯貝恵理子, 三浦郁夫, 若菜茂晴, 山口碧, 設楽浩志, 多屋長治, 木南凌, 若林雄一
    • Organizer
      第65回日本実験動物学会総会富山市富山県民会館
    • Related Report
      2018 Research-status Report
  • [Presentation] がん抑制遺伝子p19Arfに存在する非同義置換多型の機能解析2018

    • Author(s)
      斎藤慈、奥村和弘、磯貝恵理子、若林雄一
    • Organizer
      第65回日本実験動物学会総会富山市富山県民会館
    • Related Report
      2018 Research-status Report
  • [Presentation] 順遺伝学に基づくMSMマウスのがん耐性に関与する遺伝子の同定2018

    • Author(s)
      奥村和弘, 斎藤慈, 磯貝恵理子, 若林雄一
    • Organizer
      第31回モロシヌス研究会札幌市北海道大学地球環境科学研究院
    • Related Report
      2018 Research-status Report
  • [Presentation] がん抑制遺伝子p19Arfに存在する非同義置換多型の腫瘍悪性化における役割2018

    • Author(s)
      斎藤慈, 奥村和弘, 磯貝恵理子, 若林雄一
    • Organizer
      第31回モロシヌス研究会札幌市北海道大学地球環境科学研究院
    • Related Report
      2018 Research-status Report
  • [Presentation] 皮膚早期良性腫瘍抵抗性遺伝子座Stmm1aの原因遺伝子の同定2018

    • Author(s)
      奥村和弘, 斎藤慈, 磯貝恵理子, 荒木喜美, 若林雄一
    • Organizer
      第77回日本癌学会学術総会大阪市大阪国際会議場
    • Related Report
      2018 Research-status Report
  • [Presentation] p19Arfに存在する非同義置換多型の腫瘍悪性化を制御する2018

    • Author(s)
      斎藤慈, 奥村和弘, 磯貝恵理子, 荒木喜美, 若林雄一
    • Organizer
      第77回日本癌学会学術総会大阪市大阪国際会議場
    • Related Report
      2018 Research-status Report
  • [Remarks]

    • URL

      https://www.pref.chiba.lg.jp/gan/kenkyujo/soshiki/jikkendobutsu/index.html

    • Related Report
      2020 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2024-01-30  

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