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Identification of LEFTY as a molecular marker for ovarian clear cell carcinoma: its relationship to apoptosis and cell proliferation

Research Project

Project/Area Number 26860245
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Human pathology
Research InstitutionKitasato University

Principal Investigator

Matsumoto Toshihide  北里大学, 医学部, 助教 (10623184)

Research Collaborator SAEGUSA Makoto  
KODERA Yoshio  
KAWASHIMA Yusuke  
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords卵巣明細胞癌 / ショットガンプロテオミクス / Lefty / バイオマーカー / TGF-β / アポトーシス / 抗腫瘍作用 / Lefty / 子宮内膜症性卵巣嚢胞 / Smad2 / 卵巣明細胞腺癌
Outline of Final Research Achievements

We focused on Lefty, the protein identified by shotgun proteomics analysis. Lefty expression level was significantly higher in OCCCas compared with non-OCCCas. OCCCa cells stably overexpressing Lefty reduced cell proliferation, along with decreased pSmad2 expression and either activated p53/p21waf1 pathway or increased p27kip1 expression directly or indirectly. Moreover, treatment of the stable cells with cisplatin exhibited increased apoptotic cells, together with inhibition of pSmad2-mediated XIAP expression and decreased ratio of bcl2/bax. In clinical samples, a significantly higher number of apoptotic cells and lower Ki-67 LI were observed in OCCCa with high Lefty score relative to those with low score. These findings suggest that Lefty may be an excellent OCCCa-specific molecular marker, which has anti-tumor effects altering cell proliferation and susceptibility to apoptosis.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (7 results)

All 2016 2015

All Presentation (7 results)

  • [Presentation] 卵巣明細胞腺癌の発癌・進展過程におけるLeftyの機能解析2016

    • Author(s)
      松本俊英、秋谷昌史、川島祐介、小寺義男、高橋博之、三枝信
    • Organizer
      日本プロテオーム学会2016年大会
    • Place of Presentation
      北里大学薬学部白金キャンパス(東京都港区)
    • Year and Date
      2016-07-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] 卵巣癌肉腫発生過程におけるTGF-β/Smad2/Lefty系依存性上皮間葉転換機構の解析2016

    • Author(s)
      松本俊英、高橋博之、橋村美紀、梶田咲美乃、小栗康子、三枝信
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-05-12
    • Related Report
      2016 Annual Research Report
  • [Presentation] Lefty遺伝子は子宮類内膜癌細胞の分化・増殖機構の新規制御分子である2016

    • Author(s)
      木島大輝、松本俊英、橋本茉実、小栗康子、橋村美紀、三枝信
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-05-12
    • Related Report
      2016 Annual Research Report
  • [Presentation] 卵巣明細胞腺癌の発癌・進展過程におけるLeftyの機能解析2016

    • Author(s)
      秋谷昌史、山崎真瑛、松本俊英、梶田咲美乃、三枝信、川島祐介、小寺義男
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-05-12
    • Related Report
      2016 Annual Research Report
  • [Presentation] Leftyは卵巣明細胞腺癌の新規バイオマーカーである2015

    • Author(s)
      山崎真瑛、松本俊英、木島大輝、橋村美紀、鶴田智子、梶田咲美乃、高橋博之、三枝信
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-04-30
    • Related Report
      2015 Research-status Report
  • [Presentation] Leftyは正常子宮内膜および類内膜腺癌の増殖・分化を制御する2015

    • Author(s)
      木島大輝、松本俊英、山崎真瑛、橋村美紀、三枝信
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-04-30
    • Related Report
      2015 Research-status Report
  • [Presentation] β-cateninおよびPIK3CA遺伝子変異に基づく子宮内膜症性卵巣発癌の解析2015

    • Author(s)
      松本俊英、山崎真瑛、高橋博之、梶田咲美乃、鈴木エリ奈、鶴田智子、三枝信
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-04-30
    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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