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

我们报道了50%的人子宫内膜癌有肿瘤抑制基因PTEN突变。为了确定PTEN基因突变如何导致子宫内膜肿瘤的发生，我们评估了mPTEN外显子3-5缺失小鼠的子宫内膜癌。我们首先打算使用子宫内膜特异性Pten缺陷的条件靶向小鼠进行分析。然而，小鼠在分析期间患有小鼠肝炎病毒。同时对mPTEN 3-5外显子系统缺失的杂合子突变小鼠（mPTEN +/- mice）的子宫内膜进行了分析。对mPTEN +/-小鼠（n=63）和野生型小鼠（n=30）的子宫内膜进行形态学分析，直至40周龄。50%（15/30）的野生型小鼠在子宫内膜中显示轻度子宫内膜异位，7%（2/30）的小鼠显示中度子宫内膜异位。野生型小鼠均未显示子宫内膜中的严重子宫内膜炎或癌。另一方面，30%（19/63）的mPTEN +/-小鼠在子宫内膜中显示轻度子宫内膜异位，27%（17/63）显示中度子宫内膜异位，30%（19/63）显示重度子宫内膜异位。没有mPTEN+/-小鼠显示子宫内膜癌。子宫内膜重度不典型增生与子宫内膜癌前病变的复杂不典型增生相一致。提示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。

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.