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子宮内膜を標的としたPTENノックアウトマウス(子宮内膜癌モデル)の作製

Research Project

Project/Area Number 11671634
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

TASHIRO Hironori  Kumamoto University School of Medicine, Obsterics and Gynecology, Assistant Professor, 医学部・産科婦人科学講座, 助手 (70304996)

Co-Investigator(Kenkyū-buntansha) FUKUMOTO Manabu  Institute of Development, Aging and Cancer, Tohoku University, Pathology, Professor, 加齢研究所, 教授 (60156809)
SUZUKI Akira  Akita University School of Medicine, Biochemistry, Professor, 医学部・生化学, 教授 (10311565)
KATABUCHI Hidetaka  Kumamoto University School of Medicine, Obstetrics and Gynecology, Associate Professor, 附属病院産科婦人科, 講師 (90224451)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsendometrial cancer / PTEN / mouse model / Cre-loxP / heterozygous mutant mice / lacking exons 3-5 of mPTEN / complex atypical hyperplasia / Cre-lox P system / 癌抑制遺伝子
Research Abstract

We reported that 50% of human endometrial carcinoma had mutations of a tumor suppressor gene, PTEN. To determine how a mutation of PTEN gene might contribute to tumorigenesis of endometium, we assessed the endometriuin of mice lacking exons 3-5 of mPTEN. We first intended to analyze it using conditional targeting mice with endometrhim-specific Pten deficiency. However, the mice suffered from mice hepatitis virus during the analysis. Since the infected mice were cleaned up by IVF-ET method and the mice were bred again, the project has been delayed.
We simultaneously analyzed the endometrium of heterozygous mutant mice systematically lacking exons 3-5 of the mPTEN (mPTEN +/- mice). The endometrium of mPTEN +/- mice (n=63) and wild typed mice (n=30) were morphologically analyzed until 40 weeks in age. Fifty percent (15/30) of the wild typed mice showed mild atypia in the endometrium, and seven percent (2/30) did moderate atypia. None of the wild typed mice revealed severe atypia or carcinoma in the endometrium. On the other hand, thirty percent (19/63) of the mPTEN +/- mice showed mild atypia in the endometrium, twenty seven percent (17/63) did moderate atypia, and thirty percent (19/63) did severe atypia. None of the mPTEN+/- mice showed endometrial carcinoma. Severe atypia in the endometrium was consistent with complex atypical hyperplasia as a precancerous lesion in human endometrium. It was suggested that the alteration of mPTEN gene might play an important role in early event of endometrial carcinogenesis.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Lax S.F., Kendall B., Tashiro H., et al.: "The frequency of p53, K-ras mutation, and microsatellite instability differs in uterine endometrioid and serous carcinoma : evidence of distinct molecular genetic pathways"Cancer. 88. 814-824 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 片渕秀隆, 田代浩徳 他: "子宮内膜の組織分類からみた遺伝子異常の相違"産婦人科の世界. 52. 25-35 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nitta M, Katabuchi H., Ohtake H., Tashiro H., et al.: "Caracterization and tumorigenicity of human ovarian surface epithelial cells immortalized by SV40 Latge T antigen"Gyneologic Oncology. 81. 10-17 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Lax S.F., Kendall B., Tashiro H., et al.: "The frequency of p53, K-ras mutation and microsatellite instability differs in uterine endometrioid and serous carcinoma evidence of distinct molecular genetic pathway."Cancer. 88. 814-824 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nitta M., Katabuchi H., et al.: "Characterization and Tumorigenicity of Human Ovarian Surface Epithelial Cells immortalized by SV40 Large T Antigen"Gynecoligic oncology. 81. 10-17 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Lax SF., Kendall B., Tashiro H., et al.: "The frequency of p53 K-ras mutation, and microsatellite instability differs in uterine endometrioid and serous carcinoma : evidence of distinct molecular genetic pathways"Cancer. 88. 814-824 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 片渕秀隆, 田代浩徳, 他: "子宮内膜の組織分類からみた遺伝子異常の相違"産婦人科の世界. 52. 25-35 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Nitta,H.Katabuchi, et al.: "Characterization and tumorigenicity of human ovarian surface epithelial cells immortalized by SV 40 large T antigen"Gynecologic Oncology. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] SF.Lax,B.Kendall,H.Tashiro, et al.: "The frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma : evidence of distinct molecular genetic pathways"Cancer. 88. 814-824 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 片渕秀隆,田代浩徳 他: "子宮内膜癌の組織分類からみた遺伝子異常の相違"産婦人科の世界. 52. 25-35 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 片渕秀隆,荒尾慎治 他: "卵巣腫瘍における分子生物学"病理と臨床. 18. 446-454 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Lax SF,Kendall B,Tashiro H,et al.: "The frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma: evidence of distict molecular genetic pathways."Cancer. 88(4). 814-824 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tashiro H,Katabuchi H,et al.: "A follicle-stimulating hormone-secreting gonadotroph adenoma with ovarian enlargement occurring in a 10-year0old girl"Fertility and Sterility. 72. 158-160 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hata K,Kamikawa T,Arao S,Tashiro H et al.: "Expression of the thymidine phosphorylase gene in epithelial ovarian cancer"British Journal of Cancer. 79. 1848-1854 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 片淵秀隆,田代浩徳,他: "子宮内膜癌の組織分類からみた遺伝子異常の相違"産婦人科の世界. (発売予定). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 片淵秀隆,荒尾慎治,田代浩徳,他: "卵巣腫瘍における分子生物学"病理と臨床. 18巻6号(発売予定). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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