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

生成针对子宫内膜的 PTEN 基因敲除小鼠（子宫内膜癌模型）

基本信息

批准号：
11671634
负责人：
TASHIRO Hironori
金额：
$ 2.37万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671634/
关键词：
endometrial 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

项目摘要

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.

我们报道说，50％的人子宫内膜癌具有抑制肿瘤基因的突变，PTEN。为了确定PTEN基因的突变可能导致内膜的肿瘤发生，我们评估了缺乏3-5个MPTEN外显子的小鼠的子宫内膜异源。我们首先打算使用带有子宫内膜特异性PTEN缺乏症的条件靶向小鼠分析它。但是，在分析过程中，小鼠患有小鼠肝炎病毒。由于感染的小鼠通过IVF-ET方法清洁并再次育成小鼠，因此该项目已延迟。我们同时分析了杂合突变小鼠的子宫内膜，系统地缺乏MPTEN的3-5外显子（mpten +/-小鼠）。 MPTEN +/-小鼠的子宫内膜（n = 63）和野生打字小鼠（n = 30）进行形态学分析，直到年龄40周。 50％（15/30）的野生打字小鼠在子宫内膜中表现出温和的异型，而7％（2/30）的患者则为中等。野生打字的小鼠均未揭示子宫内膜中严重的异型或癌。另一方面，MPTEN +/-小鼠中有30％（19/63）在子宫内膜中表现出温和的异型，而27％（17/63）则表现为中等，而30％（19/63）发生了严重的心脏病。 MPTEN +/-小鼠均未显示子宫内膜癌。子宫内膜中的严重异型与复杂的非典型增生是人子宫内膜的癌前病变一致。有人提出，MPTEN基因的改变可能在子宫内膜癌发生的早期事件中起重要作用。