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2002 Fiscal Year Final Research Report Summary

Characterization of immortalized human ovarian surface epithelial cells transfected by PTEN expression vectors

Research Project

Project/Area Number 12671616
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKumamoto University

Principal Investigator

KATABUCHI Hidetaka  Kumamoto Univ. Sch. of Mat, OB/GYN, Associate Prof., 医学部, 助教授 (90224451)

Co-Investigator(Kenkyū-buntansha) TASHIRO Hironori  Kumamoto Univ. Sch. of Med, OB/GYN, Assistant Prof., 医学部, 助手 (70304996)
Project Period (FY) 2000 – 2002
Keywordsovarian surface epithelium / epithelial ovarian carcinoma / PTEN / LH / hCG receptor / Cip1 / Waf1 / ICAM-1 / integrin / anchorage dependent and -independent growth
Research Abstract

Epithelial ovarian carcinomas are thought to arise from cells of ovarian surface epithelium (OSE) covering the free surface of the human ovary. Two immortalized human cell lines, OSE2a (non-tumorigenic) and OSE2b-2 (tumorigenic), were previously established from normal OSE cells of a reproductive-age patient. In the present project, we found that expression of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor (R) is present in OSE2a cells and absent in OSE2b-2 cells. In OSE2a cells, a low concentration (10^3 mIU/ml) of hCG enhanced anchorage-dependent growth via up-regulation of insulin-like growth factor-1 (IGF1), whereas a high concentration (10^5 mlU/ml) of hCG induced anchorage-independent growth and down-regulation of IGF1 expression. To investigate involvement of other genes in LH/hCGR-related tumorigenicity, we compared cDNA expression arrays between OSE2a and OSE2b-2 cells, and found that the following genes had lower expression in OSE2b-2 than in OSE2a: integrin β1, intercellular adhesion molecule-1 (ICAM1), and Wafl/Cipl. Subsequent semiquantitative reverse transcription porymerase chain reaction using OSE2a cells showed that expression of integrin β1 was down-regulated by a high concentration (10^5 mlU/ml) of hCG. These results suggest that LH/CGR affects anchorage-dependent and -independent growth by mediating up- and down-regulation of IGF1 and integrin β1. Repetitive and excessive activation of LH/hCGR may cause genetic alteration of its signal transduction pathway, resulting in stimulation of growth of OSE cells, initiation of ovarian carcinogenesis, and cancer progression. We have submitted a manuscript for this study to 'Cancer Science'.
Regarding the PTEN gene, the functional analysis of LH/hCGR preceded the study for characterization of immortalized OSE cells trasfected by PTEN expression vectors. We still farther study the project for the PTEN expression.

  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] M.Nitta, H.Katabuchi et al.: "Characterization and tumorigenicity of human ovarian surface epithelial cells immortalized by SV40 large T antigen"Gynecologic Oncology. 81. 10-17 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Okamura, H.Katabuchi: "Detailed morphology of human ovarian surface epithelium focusing on its metaplastic and neoplastic capability"Italian Journal of Anatomy and Embryology. 106(Suppl 2). 263-276 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Nakayama, A.Kanzaki, K.Hata, H.Katabuchi et al.: "Hypoxia-inducible factor 1 alpha (HIF-1 alpha) gene expression in human ovarian carcinoma"Cancer Letters. 176. 215-223 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.F.Seidman, M.E.Sherman, K.A.Bell, H.Katabuchi et al.: "Salpingitis, salpingoliths, and serous tumors of the ovaries : is there a connection?"International Journal of Gynecological Pathology. 21. 101-107 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 片渕秀隆, 岡村 均: "ヒト卵巣表層上皮の生理と病理 -上皮性卵巣がんの腫瘍発生の観点から-"日本婦人科腫瘍学会雑誌. 20. 292-304 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Okamura, H.Katabuchi, T.Ohba: "What we have leamed from isolated cells from human ovary?"Molecular and Cellular Endocrinology. (In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Nitta, H. Katabuchi et al.: "Characterization and tumorigenicity of human ovarian surface epithelial cells immortalized by SV40 large T antigen"Gynecologic Oncology. 81. 10-17 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Okamura and H. Katabuchi: "Detailed morphology of human ovarian surface epithelium focusing on its metaplastic and neoplastic capability"Italian Journal of Anatomy and Embryology. 106. 263-276 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Nakayama, A. Kanzaki, K. Hata, H. Katabuchi et al: "Hypoxia-inducible factor 1 alpha (HIF-1 alpha) gene expression in human ovarian carcinoma"Cancer Letters. 176. 215-223 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J.F. Seidman, M.E. Sherman, K.A. Bell, H. Katabuchi et al.: "Salpingitis, salpingoliths, and serous tumors of the ovariesds there a connection?"International Journal of Gynecological Pathology. 20. 29-304 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Okamura, H. Katabuchi and T. Ohba: "What we have learned from isolated cells from human ovary?"Molcular and Cellular Endocrinology. Inpress. (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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