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Developmental and reproductive function of estrogen signaling

Research Project

Project/Area Number 13671162
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionSaitama Medical School

Principal Investigator

TSUKUI Tohru  Saitama Med. Sch, Dept. of Mol. Biol., Assistant Prof., 医学部, 助手 (10333006)

Co-Investigator(Kenkyū-buntansha) INOUE Satoshi  Univ. of Tokyo, Dept. of Geriatric Med., Associate Prof., 医学部附属病院, 講師 (40251251)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsEstrogen signaling / Estrogen responsive genes / Cell proliferation / Conditional transgenic / Mammary tumor / Bone metabolism / エストロゲンシグル / エストロゲシ応答遺伝子 / コンディショナルコンディショナルトランスジェニック / エストロゲンシグナル伝達 / 発生工学 / 発生生物学 / 生殖生理学 / トランスジェニックマウス / 組換えアデノウイルス / Wntシグナル
Research Abstract

Estrogen and its receptors (ERα and ERβ) are not only essential in female for normal function, but also necessary in male function such as reproductive tract, sexual behavior, maintenance of the skeleton, and cardiovascular system. In general, physiological estrogen action is regulated the transcription of estrogen responsive genes mediated by estrogen receptors. So far, the mechanism of specific estrogen action is still not clear. Simple question is what is estrogen action, and how to make specific estrogen action in vivo.
In this experiment, we have focused on gain of function in mouse in vivo by using recombinant adenovirus vector and/or conditional transgenic mice, which expressed constitutive active form human ERα and ERβ, such as ca ERα and ERβ, respectively. Alternative strategy was "conditional gain of function" by using transgenic mice with Cre/loxP system. These transgenics were expressed the reporter genes (nlsGFP/DsRed2) before treated wo/Cre recombinase, were expressed the caERα and caERβ after treated w/Cre, respectively. It was possible to activate the estrogen signaling in the timing and organs selectively, treated with Cre recombinase.
Finally, our goal is unveiled with the physiological role of estrogen signaling by through "selective gain/loss of function" in vivo. In this projects, we show that efp (estrogen responsive finger protein) is required for cell proliferation in mammary tumor by through the proteolysis 14-3-3 sigma which is negative regulator cell cycle (Nature, 417, 871-875, 2002).

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Fukuda, A, Tokonabe, S, Tsukui, T, et al., (他4名, 5番目): "Alleviation of PC4-mediated transcriptional repression by the ERCC3 helicase activity of general transcription factor TFHH"Journal of Biological Chemistry. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Urano, T, Saito, T, Tsukui, T, et al., (他5名, 3番目): "Efp targets 14-3-3sigma for proteolysis and promotes breast tumour growth"Nature. 417. 871-875 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujita, M, Urano, T, Tsukui, T, et al., (他6名, 5番目): "Estrogen activates cyclin-dependent kinases 4 and 6 through induction of cyclin D in rat primary osteoblasts"Biochem. Biophys. Res. Commun.. 299. 222-228 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujita, M, Ogawa, S, Tsukui, T, et al., (他5名, 4番目): "Differential expression of secreted frizzled-related protein 4 in decidual cells during pregnancy"Journal of Mol. Endocrinol.. 28. 213-223 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsukui, T, Toyoda, Y.: "Methods Mol. Boil. Vol.180"Humana Press. 10 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukuda A, Tokonabe S, Hamada M, Matsumoto M, Tsukui T, Nogi Y, Hisatake K: "Alleviation of PC4-mediated Transcriptional Repression by the ERCC3 Helicase Activity of General Transcription Factor TFIIH"J. Biol. Chem.. 278. 14827-14831 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Urano T, Saito T, Tsukui T, Fujita M, Hosoi T, Muramatsu M, Ouchi Y, and Inoue S: "Efp targets 14-3-3sigma for proteolysis and promotes breast tumor growth"Nature. 417. 871-875 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujita M, Ogawa S, Fukuoka H, Tsukui T, Nemoto N, Tsutsumi O, Ouchi Y, Inoue S: "Differential expression of secreted frizzled-related protein 4 in decidual cells during pregnancy"J Mol Endocrinol. 28. 213-223 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujita M, Urano T, Horie K, Ikeda K, Tsukui T, Fukuoka H, Tsutsumi O, Ouchi Y, Inoue S: "Estrogen activates cyclin-dependent kinases 4 and 6 through induction of cyclin D in rat primary"Biochem Biophys Res Commun. 299. 222-228 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsukui T, Toyoda Y: "Transgenic Techniques "Methods in Molecular Biology""Humana Press. 180. 73-82 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukuda, A, Tokonabe, S, Tsukui, T, et al., (他4名, 5番目): "Alleviation of PC4-mediated transcriptional repression by the ERCC3 helicase activity of general transcription factor TFIIH"Journal of Biological Chemistry. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Urano, T, Saito, T, Tsukui, T, et al., (他5名, 3番): "Efp targets 14-3-3sigma for proteolysis and promotes breast tumour growth"Nature. 417. 871-875 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujita, M, Urano, T, Tsukui, T, et al., (他6名, 5番目): "Estrogen activates cyclin-dependent kinases 4 and 6 through induction of cyclin D in rat primary osteoblasts"Biochem. Biophys. Res. Commun.. 299. 222-228 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujita, M, Ogawa, S, Tsukui, T, et al., (他5名, 4番目): "Differential expression of secreted frizzled-related protein 4 in decidual cells during pregnancy"Journal of Mol. Endocrinol.. 28. 213-223 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsukui, T, Toyoda, Y.: "Methods Mol. Boil. Vol. 180"Humana Press. 73-82 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mukhopadhyaya, M., Tsukui, T., (他11名, 5番目): "Dickkopfl is required for embryonic head induction and limb morphogenesis in the mouse"Developmental Cell. 1. 423-434 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujita, M., Tsukui, T., Inoue, S.(他8名, 4番目): "Differential Expression of Secreted Frizzled Related Protein 4(sFRP4) in Decidual Cells during Pregnancy"Journal of Molecular Endocrinology. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsukui, T., Toyoda, Y: "Methods in Molecuar Biology "Transgenic Techniques""Humana Press(In Press). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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