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Transcription factors of estrogen receptor alpha in human endometrium

Research Project

Project/Area Number 17591763
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionOsaka Medical College

Principal Investigator

OTSUKI Yoshinori  Osaka Medical College, Faculty of Medicine, Professor (50140166)

Co-Investigator(Kenkyū-buntansha) USHIROYAMA Takahisa  Osaka Medical College, Faculty of Medicine, a part-time lecturer (20148430)
ITOU Yuko  Osaka Medical College, Faculty of Medicine, Junior Associate Professor (40148432)
RI Churen  Osaka Medical College, Faculty of Medicine, Assistant Professor (80319532)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,180,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsestrogen / receptor / Biacore / transcription / promoter / Gel Shift Assay / exponential / extrapolation / endometrium / estrogen receptor / transcription factor / uterine / phosphorylation / apoptosis / AKT / PI3K
Research Abstract

Estrogen receptor alpha (ERα), together with estradiol plays a critical role through its target molecules in control of cell growth and differentiation. The activities of ERα itself can be modulate by epidermal growth factor (EGF), insulin-like growth factor-I via the phosphatidylinostitol 3-kinase (PI3K)/AKT pathway in breast cancer cells. To clarify how ERα functions are regulated in endometrial cells, molecules related to phosphorylation of ERα were examined. It was found that the expression of phosphorylated p-Aktl/2/3 (Thr 308) was increased during the proliferative phase, but decreased in the secretory phase. On the contrary, the expression of p-Aktl/2/3 (Thr 473) was lower in the proliferative phase, but higher after entering secretory phase. Observation of the phosphorylated Erα revealed that while the expression of p-Erα (Ser 104) was constant, p-Erα (Ser 118) was shown following a cyclic pattern like that of the p-Aktl/2/3 (Thr 308).
To reveal difference between normal and cancerous glandular cells, cultured Ishikawa cells were first examined immunohistochmically. The expression pattern of phosphorylated ERα and Akt in the untreated Ishikawa cells was similar to that of the normal endometrial cells, except that the expression of p-Erα (Ser 167) was only found in Ishikawa cells. Following treatment with various inhibitors that specifically target the ErbB/PI3K/Akt pathway, it was found out that the expression of p-Erα (Ser 118) and p-Erα (Ser 168) was inhibited. Further examination showed that inhibition of PI3K or AKT, rather than ErbB could induce apoptosis that could be antagonized by the addition of estrogen, indicating a mitochondrial pathway is involved. Further study is necessary to explore functional difference of PI3K/AKT in normal and cancerous endometrial cells.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (15 results)

All 2008 2007 2006 Other

All Journal Article (2 results) Presentation (12 results) Remarks (1 results)

  • [Journal Article] Regulation of bcl-2 transcription by estrogen receptor α in human eddometrium.

    • Author(s)
      ZL. Li, H. Abe, K. Ueki, K. Kumagai, R. Araki, Y. Otsuki
    • Journal Title

      Life Sciences (submitted)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Non-genomic regulation of estrogen receptor α functions in human endometrial cells.

    • Author(s)
      ZL. Li, H. Abe, K. Ueki, K. Kumagai, R. Araki, Y. Otsuki
    • Journal Title

      J. Histo. Biochem. (in preparation)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 粗製核蛋白中の転写因子におけるDNA結合能の自動解析2008

    • Author(s)
      李 忠連, 山本 大助, 阿部 英明, 大槻 勝紀
    • Organizer
      第113回日本解剖学会
    • Place of Presentation
      大分大学医学部
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 選択的エストロゲン受容体モジュレーターであるラロキシフェンの子宮内膜癌細胞に対するミトコンドリア経路を介するアポトーシス誘導能2008

    • Author(s)
      森嶌 祥子, 柴田 雅朗, 大道 正英, 大槻 勝紀
    • Organizer
      第113回日本解剖学会
    • Place of Presentation
      大分大学医学部
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Automatic analysis of DNA-binding activities for transcription factors in crude nuclear extracts.2008

    • Author(s)
      Zhonglian Li, Daisuke Yamamoto, Hideaki Abe, Yoshinori Otsuki
    • Organizer
      113rd Annual Meeting of the Japanese Association of Anatomists
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Induction of apoptosis through mitochondrial pathway by Raloxidene, a selective estrogenic modulator.2008

    • Author(s)
      Shoko Morishima, Masa-Aki Shibata, Masahide Omchi, Yoshinori Otsuki
    • Organizer
      113rd Annual Meeting of the Japanese Association of Anatomists
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Statistical analysis of DNA-binding activities for transcription factors in crude nuclear extracts.2008

    • Author(s)
      Zhonglian Li, Daisuke Yamamoto, Hideaki Abe, Yoshinori Otsuki
    • Organizer
      112nd Annual Meeting of the Japanese Association of Anatomists
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Analysis of SP cells in normal human endometrium.2008

    • Author(s)
      Abe Hideaki, Masaaki Shibata, Ken Kusakabe, Zhonglian Li, Yuko Ito, Shoko Morishima, Yosinori Otsuki
    • Organizer
      112nd Annual Meeting of the Japanese Association of Anatomists
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 子宮内膜癌細胞に対するraloxifeneの効果2007

    • Author(s)
      森嶌 祥子, 大道 正英, 恒遠 啓示, 西山 浩司, 山口 裕之, 金村 昌徳, 寺井 義人, 柴田 雅朗, 大槻 勝紀
    • Organizer
      第58回日本産科婦人科学会
    • Place of Presentation
      国立京都国際会館
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ヒト子宮内膜に存在するSP細胞の性状の解析2007

    • Author(s)
      阿部 英明, 柴田 雅朗, 日下 部健, 李 忠連, 伊藤 裕子, 森嶌 祥子, 大槻 勝紀
    • Organizer
      第112回日本解剖学会
    • Place of Presentation
      大阪国際会議場
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 粗製核蛋白中の転写因子におけるDNA結合能の自動解析(英語)2007

    • Author(s)
      李 忠連, 山本 大助, 阿部 英明, 大槻 勝紀
    • Organizer
      第113回日本解剖学会
    • Place of Presentation
      大阪国際会議場
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Efftcts of Raloxifene on endometrial carcinoma.2007

    • Author(s)
      Shoko Morishima, Masahide Omchi, Tsuneto Keji, Nishiyama Koji, Hiroyuki Yamaguchi, Masanori Kanemura, Yoshito Terai, Masa-Aki Shibata, Yoshinori Otsuki
    • Organizer
      58th Annual Meeting of the Japanese Association of Obstetrician gynecologists
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 女性生殖器(子宮内膜)におけるアポトーシス(特別講演)2006

    • Author(s)
      大槻 勝紀
    • Organizer
      第21回日本生殖免疫学会
    • Place of Presentation
      東京医科大学
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Apoptosis in female reproductive organ(endometrium).2006

    • Author(s)
      Yoshinori Otsuki
    • Organizer
      21st Annual Meeting of the Japanese Association of Reproductive Immunologist(Special Lecture)
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://www.osaka-med.ac.jp/deps/an1/

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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