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プロゲステロンによる卵巣腫瘍の増殖抑制のメカニズム

Research Project

Project/Area Number 15790874
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionTohoku University

Principal Investigator

赤平 純一  東北大学, 病院, 助手 (90359505)

Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywords卵巣癌 / DNAメチル化 / 14-3-3sigma / TMS1 / cyclinD2 / 精子 / 機能評価 / 精子中心体 / 顕微授精 / 受精 / Dithiothreitol / paclitaxel / プロゲステロンレセプター / 14-3-3Sigma / EBAG9
Research Abstract

【目的】卵巣癌におけるp27をはじめとする細胞周期関連遺伝子およびステロイドホルモン関連遺伝子の発現を検討するため、上皮性卵巣癌における14-3-3 sigma, TMS1, cyclin D2の発現およびその発現制御のメカニズムを検討した。
【方法】対象は当科にて初回治療を受けた上皮性卵巣癌100例および卵巣癌細胞株12株である。卵巣癌組織については14-3-3sigmaの免疫組織化学染色を行い、臨床病理学的因子との関連について検討した。卵巣癌細胞株および正常卵巣表層上皮細胞株についてはDNAのメチル化の有無をメチル化特異的PCR(MSP)、遺伝子発現をリアルタイムPCR、蛋白発現をWestern blottingにてそれぞれ行った。
【結果】14-3-3sigmaは上皮性卵巣癌100例中75例において陽性であり、進行例、漿液性腺癌において有意に発現の低下を認め、予後因子となった。(それぞれp=0.0003,0.0001,0.005)。卵巣癌細胞株においては、14-3-3sigma, TMS1, cyclin D1いずれにおいてもDNAメチル化が認められ、定量PCRによる遺伝子の発現との相関がみられた。
【結論】卵巣癌において、14-3-3sigma, TMS1, cyclin D2の発現は主としてDNAメチル化により制御されている可能性が示唆された。また、14-3-3sigma蛋白の発現低下が卵巣癌の予後不良因子となることが明らかとなった。

Report

(3 results)
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (17 results)

All 2005 2004 Other

All Journal Article (11 results) Publications (6 results)

  • [Journal Article] Expression of estrogen-responsive finger protein (Efp) is associated with advanced disease in human epithelial ovarian cance2005

    • Author(s)
      Sakuma M, Akahira J et al.
    • Journal Title

      Gynecol Oncol 99

      Pages: 664-670

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 14-3-3 sigma in endometrial cancer-a possible prognostic marker in early-stage cancer.2005

    • Author(s)
      Ito K, Akahira J et al.
    • Journal Title

      Clin Cancer Res 11

      Pages: 7384-7391

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Orphan nuclear receptor DAX-1 in human endometrium and its disorders.2005

    • Author(s)
      Saito S, Akahira J et al.
    • Journal Title

      Cancer Sci 96

      Pages: 645-652

    • NAID

      10017091008

    • Related Report
      2005 Annual Research Report
  • [Journal Article] StAR and progesterone producing enzymes (3beta HSD) and P450) in human epithelial ovarian carcinoma : immunohistochemical and real-time PCR studies2005

    • Author(s)
      Abd-Elaziz M, Akahira J et al.
    • Journal Title

      Int J Gynecol Pathol 24

      Pages: 153-163

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Primary ependymoma of the ovary : a case report and literature review2005

    • Author(s)
      Takano T, Akahira J et al.
    • Journal Title

      Int J Gynecol Cancer 15

      Pages: 1138-1141

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Promoter methylation status and expression of TMS1 gene in human epithelial ovarian cancer2004

    • Author(s)
      J Akahira et al.
    • Journal Title

      Cancer Sci 95

      Pages: 40-43

    • NAID

      10013721256

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Sentinel lymph node detection in patients with endometrial cancer2004

    • Author(s)
      H.Niikura et al.
    • Journal Title

      Gynecol Oncol 92

      Pages: 669-674

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Decreased expression of 14-3-3 sigma is associated with advanced disease in human epithelial ovarian cancer: its correlation with aberrant DNA methylation2004

    • Author(s)
      J Akahira et al.
    • Journal Title

      Clin Cancer Res 10

      Pages: 2687-2693

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer.2004

    • Author(s)
      J Akahira et al.
    • Journal Title

      Birt J Cancer 90

      Pages: 2197-2202

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Sentinel lymph node detection in early cervical cancer with combination 99mTc phytate and patent blue.2004

    • Author(s)
      H Niikura et al.
    • Journal Title

      Gynecol Oncol 94

      Pages: 528-532

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Clinical experience with combination paclitaxel and carboplatin therapy for advanced of recurrent carcinosarcoma of the uterus.2004

    • Author(s)
      M Toyoshima et al.
    • Journal Title

      Gynecol Oncol 94

      Pages: 774-778

    • Related Report
      2004 Annual Research Report
  • [Publications] Akahira J, Aoki M, Suzuki T, Moriya T, Niikura H, Ito K, Inoue S, Okamura K, Sasano H, Yaegashi N: "Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer."Brit J Cancer. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akahira J, Sugihashi Y, Suzuki T, Ito K, Niikura H, Moriya T, Nitta M, Okamura K, Inoue S, Sasano H, Okumura K, Yaegashi N: "Decreased expression of 14-3-3 sigma is a prognostic factor in human epithelial ovarian cancer : Its correlation with aberrant DNA methylation."Clin Cancer Res. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akahira J, Konno R, Ito K, Okumura K, Yaegashi N: "Impact of serum Interleukin-18 level as a prognostic indicator in patients with epithelial ovarian carcinoma."Int J Clin Oncol. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akahira J, Sugihashi Y, Ito K, Niikura H, Okamura K, Yaegashi N: "Promoter methylation status and expression of TMS1 gene in human epithelial ovarian cancer."Cancer Sci.. 95. 40-43 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Abd-Elaziz M, Akahira J, Moriya T, Suzuki T, Yaegashi N, Sasano H: "Nuclear receptor DAX-1 in human common epithelial ovarian carcinoma: An independent prognostic factor of clinical outcome."Cancer Sci.. 94. 980-985 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kimura Y, Suzuki T, Kaneko C, Darnel AD, Akahira J, Ebina M, Nukiwa T, Sasano H: "Expression of androgen receptor and 5alpha-reductase types 1 and 2 in early gestation fetal lung : a possible correlation with branching morphogenesis."Clin Sci (Lond). 105. 709-713 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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