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的突变。为了确定PTEN基因突变如何促进子宫内膜的肿瘤发生，我们评估了缺乏mPTEN外显子3-5的小鼠的子宫内膜激素。我们首先打算用子宫内膜特异性Pten缺乏的条件靶向小鼠来分析它。然而，在分析过程中，小鼠感染了小鼠肝炎病毒。由于感染小鼠已通过IVF-ET方法清理干净并重新繁殖，因此项目被推迟。我们同时分析了缺乏mPTEN外显子3-5的杂合突变小鼠（mPTEN +/-小鼠）的子宫内膜。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）野生型小鼠的子宫内膜表现为轻度异型，7%（2/30）表现为中度异型。野生型小鼠均未出现严重的异型性或子宫内膜癌。另一方面，30%（19/63）的mPTEN +/-小鼠子宫内膜表现为轻度异型，27%（17/63）表现为中度异型，30%（19/63）表现为严重异型。mPTEN+/-小鼠均未出现子宫内膜癌。子宫内膜的严重异型性与人类子宫内膜癌前病变的复杂非典型增生一致。提示mPTEN基因的改变可能在子宫内膜癌的早期发生中起重要作用。

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.