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Mechanism of Granulosa Cell Differentiation and Oncogenesis

Research Project

Project/Area Number 10044255
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionFUKUI MEDICAL UNIVERSITY, DEPARTMENT OF OBSTETRICS AND GYNECOLOGY

Principal Investigator

KOTSUJI Fumikazu  Fukui Medical University, Dept. of OB/GYN, Professor, 医学部, 教授 (50153573)

Co-Investigator(Kenkyū-buntansha) YOSHIDA Yoshio  Fukui Medical University, Dept. of OB/GYN, Instructor, 医学部, 助手 (60220688)
TAJIMA Kimihisa  Fukui Medical University, Dept. of OB/GYN, Instructor, 医学部・附属病院, 助手 (60303377)
HOSOKAWA Kumiko  Fukui Medical University, Dept. of OB/GYN, Assistant Professor, 医学部, 講師 (60199495)
YONEKURA Yoshiharu  Fukui Medical University, Biomedical Imaging Center, Professor, 高エネルギー医学研究センター, 教授 (60135572)
SASAKI Hiromasa  Fukui Medical University, Dept. of OB/GYN, Instructor, 医学部, 助手 (20225890)
TSNG Benjami  University of Ottawa Department of Obste, Professor
AMSTERDAM Ab  The Weizmann Institute of Science Depart, Associate
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥3,400,000 (Direct Cost: ¥3,400,000)
KeywordsGranulosa Cell / Differentiation / Apoptosis / Progesterone / Oncogenesis / cisplatin / theophylline / Ovarian Cancer / Xiap / ステロイド産生 / p53 / Mdm2 / シスプラチン / 上皮性卵巣癌細胞
Research Abstract

1. Molecular mechanism of steroidogenesis and apoptosis in human granulosa cells.
Using human granulosa cell lines (HO-23), it was confirmed that glucocorticoids and extracellular matrix(ECM) enhanced P4 production while bFGF and phorbol ester TPA suppressed it, that glucocorticoids, ECM and bFGF inhibited p53-induced apoptosis of HO-23 cells while TPA enhanced it, and that apoptosis at early stage does not interrupt steroidogenesis.
2. Establishment of a new treatment strategy for ovarian cancer:
(1) The Efficacy of combination of cisplatin and theophylline:
We have found that cisplatin synergies with theophylline in induction of cell death in human ovarian cancerous cells with mutated p53 and HaRAS (HRP-53) in concentrations lower 3-5 times than these normally administered in ovarian cancer therapy.
(2) We have demonstrated that Xiap down-regulation in p53 wild-type resistant human ovarian cancer cells induces caspase-3-mediated MDM2 processing, leading to increased p53 content and apoptosis. While ineffective alone in p53-mutant cancer cells, suppression of Xiap content by antisense expression can significant enhance the pro-apoptoic effects of wild type-p53 sense expression. In addition, these findings suggest that Xiap may be a novel target.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report

Research Products

(22 results)

All Other

All Publications (22 results)

  • [Publications] 細川久美子ら: "ヒト顆粒膜細胞株の樹立とこれを用いたホルモン産生アポトーシス発現機序の研究"産婦人科治療. 78. 1172 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H Yada et al: "The role of ovarian theca and granulosa cell interaction in hormone production and cell growth during the bovine follicular maturation process"Biol Reprod. 61. 1480-1486 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A Amsterdam et al: "Structure-function relationship in the normal and malignant ovary during programmed cell death"Acta Histochem Cytochem. 32. 127-131 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A Amsterdam et al: "Crosstalk among multiple signaling pathways controlling ovarian cell death"Trend in Endocrinology and Metabolism. 10. 255-261 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H Sasaki et al: "Apoptosis and Chemoresistance in human ovarian cancer"Biological Signals and Receptors. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H Sasaki et al: "Frontiers in Endocrinology Ovarian Function Research : Present and Future"Serono Symposia Publications. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H Yada et al: "The role ovarian theca and granulosa cell interaction in hormone production and cell growth during the bovine follicular maturation process."Biol Reprod. 61. 1480-1486 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A Amsterdam et al: "Structure-function relationship in the normal and malignant ovary during programmed cell death"Acta Histochem Cytochem. 32(2). 127-131 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A Amsterdam et a.l: "Crosstalk among multiple signaling pathways controlling ovarian cell death"Trend in Endocrinology and Metabolism. 10(7). 255-261 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H Sasaki et al: "Apoptosis and Chemoresistance in human ovarian cancer"Biological Signals and Receptors. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H Sasaki et al: "Frontiers in Endocrinology Ovarian Function Research: Present and Future"Serono Symposia Puburications. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 細川 久美子ら: "ヒト顆粒膜細胞株の樹立とこれを用いたホルモン産生アポトーシス発現機序の研究"産婦人科治療. 78・6. 1172 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H. Yada, et al.: "The role of ovarian theca and granulosa cell interaction in hormone production and cell growth during the bovine follicular maturation process."Biol Reprod. 61. 1480-1486 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] A Amsterdam, et al.: "Structure-function relationship in the normal and malignant ovary during programmed cell death."Acta Histochem Cytochem. 32・2. 127-131 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] A Amsterdam, et al.: "Crosstalk among multiple signaling pathways controlling ovarian cell death."Trend in Endocrinology and Metabolism. 10・7. 255-261 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H. Sasaki, et al.: "Apoptosis and Chemoresistance in human ovarian cancer."Biological Signals and Receptors.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Sasaki, H. et al.: "Frontiers in Endocrinology Ovarian Function Research : Present and Future"Serono Symposia Puburications. (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 細川久美子ら: "Steroid regulation during apoptosis of ovarian follicular cells." Steroids. 63巻. 1-5 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 細川久美子ら: "Induction of Ad4BP/SF-1,steroidogenic acute regulatory protein,and cytochrome P450scc enzyme system expression in newly established human granulosa cell lines." Endocrinology. 139巻. 4679-4687 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 細川久美子ら: "Modulation of Mdm2 expression and p53-induced apoptosis in immortalized human ovarian granulosa cells." Endocrinology. 139巻. 4688-4700 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 佐々木博正ら: "Life,death and immortality;cellular and molecular prspectives in human ovarian cancer cell growth." Frontiers in the Research of Ovarian Function. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] 吉田好雄ら: "Structure-function relationship in the normal and malignant ovary during programmed cell death." Acta Histochem Cytochem. (in press).

    • Related Report
      1998 Annual Research Report

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Published: 1998-03-31   Modified: 2016-04-21  

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