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2005 Fiscal Year Final Research Report Summary

Influence of endocrine disturbance in endometrial carcinogenesis in recombinant PTEN mice.

Research Project

Project/Area Number 15591764
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, University Hospital, Assistant Professor, 医学部附属病院, 講師 (70304996)

Co-Investigator(Kenkyū-buntansha) KATABUCHI Hidetaka  Kumamoto University, Faculty of Medical and pharmaceutical Sciences, Professor, 大学院・医学薬学研究部, 教授 (90224451)
Project Period (FY) 2003 – 2005
KeywordsPTEN recombinant mice / Endometrial carcinoma / Endometrial stroma / Hoxa 10 gene / Hoxa 11 gene / Hyalinization of stroma / Atrophic stroma / 内膜間質萎縮
Research Abstract

Human endometrial carcinomas, as well as complex atypical hyperplasias (CAH), are estrogen-related and frequently have mutations in the PTEN gene. However, the mutual contribution of estrogen and PTEN mutations to endometrial carcinogenesis in vivo is unknown. To address this issue, we investigated whether neonatal estrogenic treatments augment the incidence of CAH and carcinomas in mPTEN heterozygous (+/-) mutant mice, an animal model for endometrial carcinoma. Low doses of diethylstilbestrol (1 ng/g/day), genistein (50 μg/g/day) in phytoestrogens, estriol (E_3) (4 μg/g/day) and vehicle (ethanol and corn oil) were administered subcutaneously daily to neonatal pups from the 1st to 5th day after birth. At 52 weeks of age, the morphological changes in endometrium, and uterine expression of Hoxa 10 and Hoxa 11, were evaluated. These Hoxa genes are abdominal B type homeobox genes, which normally regulate differentiation of the mullerian duct. The incidence of CAH and adenocarcinomas of the endometrium was significantly decreased by the neonatal estrogenic treatments in the mPTEN+/- mice. Coincidentally, all treatments significantly decreased the stromal cell density, and CAH and adenocarcinomas rarely developed in the epithelium adjacent to the affected endometrial stroma. Moreover, the uterine expression of Hoxa 10 in mice with neonatal genistein and E_3 treatments, and that of Hoxa 11 in mice with all treatments, was significantly lower when compared with vehicle alone. Taken together, neonatal estrogenic exposure induced stromal atrophy and/or hyalinization accompanied by repressed expression of Hoxa 10 and Hoxa 11, and exerted an inhibitory effect on PTEN-related tumorigenesis. These findings provide new insight into the interaction between endometrial epithelium and stroma in endometrial carcinogenesis in vivo.

  • Research Products

    (7 results)

All 2006 2005

All Journal Article (7 results)

  • [Journal Article] Neonatal estrogenic exposure suppresses PTEN-related endometrial carcinogenesis in recombinant mice.2006

    • Author(s)
      Begum M, Tashiro H, Katabuchi H, Suzuki A, Kurman RJ, et al.
    • Journal Title

      Lab Invest 86

      Pages: 286-296

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Characterization of 17beta-hydroxysteroid dehydrogenase type4 in human ovarian surface epithelial cells.2006

    • Author(s)
      Nagayoshi Y, Ohba T, Yamamoto H, Miyahara Y, Tashiro H et al.
    • Journal Title

      Mol Hum Reprod 11

      Pages: 615-621

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Neonatal estrogenic exposure suppresses PTEN-related endometrial carcinogenesis in recombinant mice.2006

    • Author(s)
      Begum M, Tashiro H, Katabuchi H, Suzuki A, Kurman RJ, Okamura H.
    • Journal Title

      Lab Invest 86

      Pages: 286-296

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Characterization of 17beta-hydroxysteroid dehydrogenase type 4 in human ovarian surface epithelial cell.2006

    • Author(s)
      Nagayoshi Y, Ohba T, Yamamoto H, Miyahara Y, Tashiro H, Katabuchi H, et al.
    • Journal Title

      Mol Hum Reprod 11

      Pages: 615-621

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Establishment of an immortalised human ovarian surface epithelial cell line without chromosomal instability.2005

    • Author(s)
      Maeda T, Tashiro H, Katabuchi H, Begum M, Ohtake H, et al.
    • Journal Title

      Br J Cancer 93

      Pages: 116-123

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression of variant luteinizing hormone/chorionic gonadotropin receptors and degradation of chorionic gonadotropin in human chorionic villous macrophages.2005

    • Author(s)
      Sonoda N, Katabuchi H, Tashiro H,, et al.
    • Journal Title

      Placenta 26

      Pages: 298-307

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Establishment of an immortalised human ovarian surface epithelial cell line without chromosomal instability.2005

    • Author(s)
      Maeda T, Tashiro H, Katabuchi H, et al.
    • Journal Title

      Br J Cancer 93

      Pages: 116-123

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

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Published: 2007-12-13  

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