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子宮内膜症の発生および癌化機構の解明

Research Project

Project/Area Number 20659259
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionJuntendo University (2009)
Kyushu University (2008)

Principal Investigator

加藤 聖子  Juntendo University, 医学部, 准教授 (10253527)

Co-Investigator(Kenkyū-buntansha) 内田 聡子  九州大学, 大学病院, 助教 (30380611)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2008: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywords子宮内膜症 / Ras / エストロゲンレセプター / アポトーシス / 内膜幹細胞
Research Abstract

我々は以前ヒト正常子宮内膜よりSide Population細胞を分離しSP細胞が長期増殖能を持ち内膜腺上皮や間質細胞への分化能を有すること、このSP細胞の割合は月経期内膜に最も高いことを報告した。子宮内膜症の発症を月経血逆流説から検討するため、インフォームドコンセントを得た患者から月経血を採取し内膜細胞を分離培養しSP細胞を分離しその増殖能を解析した。月経血中の内膜細胞にはSP細胞が存在した(n=5,平均0.704%)。このSP細胞およびnon SP細胞を分離培養し、増殖能を解析したところ、SP細胞の増殖能が亢進されていた。また、コラーゲンプレートに500 cells/cm^2の細胞を播種したところ、SP細胞のみでコロニーが形成され、このコロニーより分離された細胞は同様にコラーゲンプレート上にコロニーを形成した(自己複製能)。また、昨年度ラット子宮内膜細胞のSP細胞とnon SP細胞を用いたマイクロアレイによりSP細胞で有意に発現の高かった受容体蛋白を蛍光免疫染色で解析すると、月経血中子宮内膜のSP細胞にnon SP細胞に比べ陽性細胞数が多かった。以上より、月経血中の子宮内膜細胞に、増殖能の高い、コロニー形成能、自己複製能を有する細胞が存在することが明らかになった。この細胞群が異所性に増殖する性質を持っ子宮内膜症の発生機構に関与する可能性が示唆された。
内膜症からの癌化機構を検討するため、内膜症と卵巣癌(明細胞腺癌)が共存する組織切片を用いて、子宮体癌SP細胞で発現が増加していた蛋白の発現を免疫染色法で解析した。この蛋白発現は卵巣癌近傍の子宮内膜症に強く発現されていたが、離れた部位の内膜症組織や正常内膜には発現していなかった。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (24 results)

All 2010 2009 2008

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (11 results)

  • [Journal Article] Low-dose mithramycin exerts its anti-cancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers2010

    • Author(s)
      Ohgami T, Kato K, Kobayashi H, Sonoda K, Inoue T, Yamaguchi S, Yoneda T, Wake N.
    • Journal Title

      Cancer Sci (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Specific regulation of point-mutated K-ras-immortalized cell proliferation by a photodynamic antisense strategy2010

    • Author(s)
      Higuchi M, Yamayoshi A, Kato K, Kobori A, Wake N, Murakami A.
    • Journal Title

      Oligonucleotides 20

      Pages: 37-44

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endometrial cancer side-population cells show prominent migration and have a potential to differentiate into the mesenchymal cell lineage2010

    • Author(s)
      Kato K, Takao T, Kuboyama A, Tanaka Y, Ohgami T, Yamaguchi S, Adachi S, Yoneda T, Ueoka Y, Kato K, Hayashi S, Asanoma K, Wake N.
    • Journal Title

      Am J Pathol 176

      Pages: 381-392

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Level of reactive oxygen species induced by p21Waf1/CIP1 is critical for the determination of cell fate2009

    • Author(s)
      Inoue T, Kato K, Kato H, Asanoma K, Kuboyama A, Ueoka Y, Yamaguchi S, Ohgami T, Wake N.
    • Journal Title

      Cancer Sci. 100

      Pages: 1275-1248

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of haplotype inference using definitive haplotype data obtained from complete hydatidiform moles, and its significance for the analyses of positively selected regions2009

    • Author(s)
      Higasa K, Kukita Y, Kato K, Wake N, Tahira T, Hayashi K.
    • Journal Title

      PLoS Genet. 5

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of senescence by progesterone receptor-B activation in response to cAMP in ovarian cancer cells2009

    • Author(s)
      Takahashi A, Kato K, Kuboyama A, Inoue T, Tanaka Y, Kuhara A, Kinoshita K, Takeda S, Wake N.
    • Journal Title

      Gynecol Oncol. 113

      Pages: 270-276

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Homeobox gene HOPX is epigenetically silenced in human uterine endometrial cancer and suppresses estrogen-stimulated proliferation of cancer cells by inhibiting serum response factor2009

    • Author(s)
      Yamaguchi S, Asanoma K, Takao T, Kato K, Wake N.
    • Journal Title

      Int J Cancer. 124

      Pages: 2577-2588

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Homeobox gene NECCI is epigenetically silenced in human uterine endometrial cancer and suppresses edtrogen-stimulated proliferation of cancer cells by inhibiting serum response factor2009

    • Author(s)
      Yamaguchi S, et al.
    • Journal Title

      Int J Cancer 124(11)

      Pages: 2577-2588

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of senescence by progesterone receptor -B activation in response tocAMP in ovarian cancer cells2009

    • Author(s)
      Takahashi A, et al.
    • Journal Title

      Gynecol Oncol 113

      Pages: 270-276

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The level of reactive oxygen species induced by p21 WAF1/CIP1 is critical the determination of cell fate2009

    • Author(s)
      Inoue T, et al.
    • Journal Title

      Cancer Sci in press

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of haplotype inference using definitive haplotype dataobtained from complete hydatidiform moles, and its significance for the analyses of positively selected regions2009

    • Author(s)
      Higasa K, et al.
    • Journal Title

      PLoS Genetics in press

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Medroxyprogesterone acetate inhibits proliferation of colon cancer cell lines by modulating cell cycle-related protein expression2008

    • Author(s)
      Tanaka Y, et al.
    • Journal Title

      Menopause 15

      Pages: 442-453

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interstitial pregnancy in a woman with congenital afibrinogenemia2008

    • Author(s)
      Matsushita I, et al.
    • Journal Title

      J Obstet Gynaecol Res 34(5)

      Pages: 914-918

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Progesterone Receptor-Bの活性化を介する卵巣癌増殖抑制機構の解析2009

    • Author(s)
      加藤聖子, 井上貴史, 米田智子, 大神達寛, 山口真一郎, 和氣徳夫
    • Organizer
      第61回日本産科婦人科学会・学術講演会
    • Place of Presentation
      京都市
    • Related Report
      2009 Annual Research Report
  • [Presentation] Endometrial cancer side-population cells show prominent migration and have a potential to differentiate into the mesenchymal cell lineage2009

    • Author(s)
      加藤聖子
    • Organizer
      第61回日本フローサイトメトリー学会
    • Place of Presentation
      松江市
    • Related Report
      2009 Annual Research Report
  • [Presentation] 子宮体癌の発生要因(遺伝子多型、環境要因)に関する症例、対照研究2009

    • Author(s)
      米田智子, 加藤聖子, 久保山歩美, 齋藤俊章, 古野純典, 和氣徳夫
    • Organizer
      第46回日本婦人科腫瘍学会学術集会
    • Place of Presentation
      新潟市
    • Related Report
      2009 Annual Research Report
  • [Presentation] 子宮体癌細胞の stem like cell の同定と生物学的特性の解析2009

    • Author(s)
      加藤聖子
    • Organizer
      第27回日本ヒト細胞学会学術集会
    • Place of Presentation
      東京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] 子宮体癌幹細胞は著明な運動能亢進と間葉系細胞への分化を示す2009

    • Author(s)
      加藤聖子, 和氣徳夫
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜市
    • Related Report
      2009 Annual Research Report
  • [Presentation]2009

    • Author(s)
      加藤聖子
    • Organizer
      第48回日本臨床細胞学会秋期大会
    • Place of Presentation
      福岡市
    • Related Report
      2009 Annual Research Report
  • [Presentation] Endometrial cancer side population cells show charasteristics of cancer stem-like cell2008

    • Author(s)
      Kato K, et al.
    • Organizer
      第60回日本産科婦人科学会総会・学術講演会
    • Place of Presentation
      横浜市
    • Related Report
      2008 Annual Research Report
  • [Presentation] 子宮体癌細胞のstem like cellの同定と生物学的特性の解析2008

    • Author(s)
      加藤 聖子, 他
    • Organizer
      第49回日本臨床細胞学会総会(春季大会)
    • Place of Presentation
      東京都
    • Related Report
      2008 Annual Research Report
  • [Presentation] エストロゲンレセプターを標的としたデコイ核酸によるヒト乳癌細胞増殖制御2008

    • Author(s)
      山吉 麻子, 他
    • Organizer
      第12回がん分子標的治療研究会総会
    • Place of Presentation
      東京都
    • Related Report
      2008 Annual Research Report
  • [Presentation]2008

    • Author(s)
      加藤 聖子, 他
    • Organizer
      ヒト正常子宮内膜stem like cellの同定と解析
    • Place of Presentation
      神戸市
    • Related Report
      2008 Annual Research Report
  • [Presentation] Epithelial to mesenchymal transition is an important phenotype of endometrial cancer stem-like cells2008

    • Author(s)
      Kato K, et al.
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋市
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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