2001 Fiscal Year Final Research Report Summary
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
| Project/Area Number |
11671634
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kumamoto University |
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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)
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| 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)
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| Project Period (FY) |
1999 – 2001
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| Keywords | endometrial cancer / PTEN / mouse model / Cre-loxP / heterozygous mutant mice / lacking exons 3-5 of mPTEN / complex atypical hyperplasia |
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| 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.
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