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Meis1 regulates epidermal stem cells and is required for skin tumorigenesis

Research Project

Project/Area Number 23590454
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionChiba Cancer Center (Research Institute)

Principal Investigator

WAKABAYASHI Yuichi  千葉県がんセンター(研究所), 実験動物研究室, 室長 (40303119)

Co-Investigator(Kenkyū-buntansha) 奥村 和弘  千葉県がんセンター研究所 (80584680)
Co-Investigator(Renkei-kenkyūsha) 後飯塚 僚  東京理科大学 (50301552)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords発がん / 幹細胞 / 表皮 / 化学発がん / Meis1 / アメリカ合衆国 / 表皮幹細胞
Research Abstract

We uncover two roles for Meis1 in the epidermis: as a critical regulator of epidermal homeostasis in normal tissues and as a proto-oncogenic factor in neoplastic tissues. In normal epidermis, we show that Meis1 is predominantly expressed in the bulge region of the hair follicles where multipotent adult stem cells reside, and that the number of these stem cells is reduced when Meis1 is deleted in the epidermal tissue of mice. Mice with epidermal deletion of Meis1 developed significantly fewer DMBA/TPA-induced benign and malignant tumors compared with wild-type mice, suggesting that Meis1 plays a role in both tumor development and malignant progression. This is consistent with the observation that Meis1 expression increases as tumors progress from benign papillomas to malignant carcinomas.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (22 results)

All 2014 2013 2012 2011 Other

All Journal Article (11 results) (of which Peer Reviewed: 4 results) Presentation (9 results) (of which Invited: 1 results) Remarks (2 results)

  • [Journal Article] Congenic mapping and allele-specific alteration analysis of Stmm1 locus conferring resistance to early-stage chemically induced skin papillomas2014

    • Author(s)
      Okumura K, Saito M, Isogai E, Miura I, Wakana S, Kominami R, and Wakabayashi Y
    • Journal Title

      PLoS One

      Volume: 9 (5)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Identification of Stmm3 locus conferring resistance to late-stage chemically induced skin papillomas on mouse chromosome 4 by congenic mapping and allele-specific alteration analysis.2014

    • Author(s)
      Saito M, Okumura K, Miura I, Wakana S, Kominami R, and Wakabayashi Y.
    • Journal Title

      Experimental Animals

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiple Self-Healing Squamous Epithelioma (MSSE): Rare Variants in an Adjacent Region of Chromosome 9q22.3 to Known TGFBR1 Mutations Suggest a Digenic or Multilocus Etiology2013

    • Author(s)
      Chung Kang H, Quigley DA, Kim IJ, Wakabayashi Y, Ferguson-Smith MA, D'Alessandro M, Birgitte Lane E, Akhurst RJ, Goudie DR, Balmain A
    • Journal Title

      J Invest Dermatol

      Volume: 133 Pages: 1907-1910

    • Related Report
      2013 Final Research Report
  • [Journal Article] Ptch overexpression drives skin carcinogenesis and developmental defects in K14PtchFVB mice2013

    • Author(s)
      Kang HC, Wakabayashi Y, Jen KY, Mao JH, Del Rosario R, and Balmain A
    • Journal Title

      J Invest Dermatol

      Volume: 133 (5) Pages: 1311-1320

    • Related Report
      2013 Final Research Report
  • [Journal Article] Multiple Self-Healing Squamous Epithelioma (MSSE): a digenic or multilocus trait caused by TGFBR1 mutations and rare variants in an adjacent region of chromosome 9q22.32013

    • Author(s)
      Kang, H.C., Quigley, D., Kim, I.J., Wakabayashi, Y., Dunlop, M., Ferguson-Smith, M.A., Goudie, D.R., Balmain, A.
    • Journal Title

      J. Invest. Dermatol.

      Volume: 133 Issue: 7 Pages: 1907-1910

    • DOI

      10.1038/jid.2013.45

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PTCH overexpression drives skin carcinogenesis and developmental defects in K14 PTCHFVB mice2013

    • Author(s)
      Kang, H.C., Wakabayashi, Y., Jen, K.Y., Mao, J.H., Del-Rosario, R., Balmain, A.
    • Journal Title

      J. Invest. Dermatol.

      Volume: 133 Issue: 5 Pages: 1311-1320

    • DOI

      10.1038/jid.2012.419

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Independent genetic control of early and late stages of chemically induced skin tumors in a cross of a Japanese wild derived inbred strain, MSM/Ms2012

    • Author(s)
      Okumura K, Sato M, Miura I, Wakana S, Mao JH, Miyasaka Y, Kominami R, and Wakabayashi Y
    • Journal Title

      Carcinogenesis

      Volume: 33 (11) Pages: 2260-2268

    • Related Report
      2013 Final Research Report
  • [Journal Article] Independent genetic control of early and late stages of chemically induced skin tumors in a cross of a Japanese wild derived inbred mouse strain, MSM/Ms2012

    • Author(s)
      Okumura K, Sato M, Ikuo M, Wakana S, Mao JH, Miyasaka Y, Kominami R, and Wakabayashi Y.
    • Journal Title

      Carcinogenesis

      Volume: 33 Issue: 11 Pages: 2260-2268

    • DOI

      10.1093/carcin/bgs250

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 日本産野生マウス、モロシヌスを用いた発がん感受性遺伝子座の探索2011

    • Author(s)
      若林雄一
    • Journal Title

      新潟医師会報

      Volume: 733 Pages: 2-4

    • Related Report
      2011 Research-status Report
  • [Journal Article] Meis1 regulates epidermal stem cells and is required for skin tumorigenesis

    • Author(s)
      Okumura K , Saito M, Aoto Y, Hachiya T, Sakakibara Y, Katsuragi Y, Hirose S, Kominami R, Goitsuka R, Nakamura T and Wakabayashi Y
    • Journal Title

      PLoS One

      Volume: (in press)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Identification of Stmm3 locus conferring resistance to late-stage chemically induced skin papillomas on mouse chromosome 4 by congenic mapping and allele-specific alteration analysis

    • Author(s)
      Saito M, Okumura K, Miura I, Wakana S, Kominami R, and Wakabayashi Y
    • Journal Title

      Experimental Animals

      Volume: (in press)

    • Related Report
      2013 Final Research Report
  • [Presentation] Meis1は表皮幹細胞の維持と皮膚発がんに必要である2013

    • Author(s)
      奥村和弘、齋藤慈、青戸良賢、八谷剛史、榊原康文、葛城美徳、廣瀬哲史、木南凌、後飯塚僚、中村卓郎、若林雄一
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-04
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Meis1は腫瘍悪性化を制御する2013

    • Author(s)
      奥村和弘、齋藤慈、大澤光次郎、廣瀬哲史、木南凌、後飯塚僚、中村卓郎、若林雄一
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-04
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Meis1の腫瘍悪性化プロセスにおける役割2013

    • Author(s)
      齋藤慈、奥村和弘、八谷剛史、榊原康文、大澤光次郎、岩間厚志、廣瀬哲史、木南凌、後飯塚僚、中村卓郎、若林雄一
    • Organizer
      第27回モロシヌス研究会
    • Place of Presentation
      つくば
    • Year and Date
      2013-06-29
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 皮膚正常/がん幹細胞におけるMeis1の機能解析2012

    • Author(s)
      奥村和弘
    • Organizer
      第26回モロシヌス研究会
    • Place of Presentation
      東京本郷
    • Year and Date
      2012-06-16
    • Related Report
      2013 Final Research Report
  • [Presentation] Meis1は皮膚毛包幹細胞の維持に重要である2012

    • Author(s)
      奥村和弘、佐藤美穂、廣瀬哲史、後飯塚僚、中村卓郎、若林雄一
    • Organizer
      第59回日本実験動物学会年会
    • Place of Presentation
      別府
    • Year and Date
      2012-05-24
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] Meis1遺伝子の表皮幹細胞における機能の解析2012

    • Author(s)
      若林雄一
    • Organizer
      マウス遺伝学研究集会・マウス遺伝学の進歩
    • Place of Presentation
      新潟
    • Year and Date
      2012-03-02
    • Related Report
      2013 Final Research Report
  • [Presentation] 表皮幹細胞におけるMeis1遺伝子の機能解析2011

    • Author(s)
      奥村和弘、佐藤美穂、広瀬哲史、後飯塚僚、中村卓郎、若林雄一
    • Organizer
      第58回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Functional Analysis of Meis1 in Epidermal Stem Cell of mice.2011

    • Author(s)
      Yuichi Wakabayashi
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] 腫瘍悪性化プロセスを制御する遺伝子群の探索

    • Author(s)
      若林雄一
    • Organizer
      平成24年度国立遺伝学研究所研究集会
    • Place of Presentation
      静岡・三島
    • Related Report
      2012 Research-status Report
    • Invited
  • [Remarks]

    • URL

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

    • Related Report
      2013 Final Research Report
  • [Remarks] 千葉県がんセンター研究所実験動物研究室

    • URL

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

    • Related Report
      2013 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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