Analysis of mechanism of carcinogenesis in uterine cervix of K5 E2F1 transgenic mice

“高危”人乳头瘤病毒（HPV），如HPV-16和-18，在80-90%的宫颈浸润性癌中发现。然而，HPV感染似乎是不足以致癌，因为大多数病变的人宫颈鳞状上皮细胞含有高风险的HPV不进展为浸润性癌。此外，一些研究人员报告说，HPV或E6/E7转基因小鼠发生宫颈上皮内瘤变，但不是浸润性癌症。提示除HPV感染外，其他基因的改变也可能是宫颈癌发生的重要因素。近年来，我们利用特异性角蛋白启动子建立了许多转基因小鼠，这些小鼠发生了包括皮肤、前列腺和胆囊在内的各种上皮性肿瘤。在我们最近的研究中，宫颈鳞状上皮表达K1，K5和K14，鳞状-柱状交界处的储备细胞表达K5。这些结果表明， ...更多信息 使用特异性角蛋白启动子的转基因小鼠子宫颈中可能过量表达内斯。在这项研究中，我们分析了我们的各种转基因小鼠的雌性生殖道，最终我们发现K5 E2 F1转基因小鼠发生了子宫颈癌。E2 F1，以及角蛋白5，过度表达在鳞状上皮细胞的子宫颈和癌组织从K5 E2 F1转基因小鼠。通常，作为理想的适当的癌症动物模型的要求，在这样的模型中发展的肿瘤必须显示出与人类癌症的合理程度的相似性。来自K5 E2 F1转基因小鼠的宫颈癌与人宫颈癌相似，如下：i）它们是鳞状细胞癌。ii）它们由类似的前驱病变，宫颈上皮内瘤变（CIN）发展而来。这些结果提示K5 E2 F1转基因小鼠是研究宫颈癌发生的理想动物模型。少

The "high-risk" human papilloma viruses (HPVs), such as HPV-16 and-18, are found in 80-90% of invasive cancers of the uterine cervix. However, HPV-infection appears to be insufficient for carcinogenesis, because most lesions in human cervical squamous epithelium containing high-risk HPVs do not progress to invasive carcinoma. Furthermore, several researchers reported that HPV or E6/E7 transgenic mice developed cervical intraepithelial neoplasias, but not invasive cancers. These evidences suggested that the other genetic alterations in addition to HPV-infection might be also important for cervical carcinogenesis. Recently, we have established a lot of transgenic mice using specific keratin promoters, which developed various epithelial tumors including skin, prostate and gallbladder. In our more recent studies, the squamous epithelium of uterine cervix expressed K1, K5 and K14, and the reserve cells at the squamo-columnar junction had K5 expression. These results suggested that target ge … More nes might be overexpressed in uterine cervix of transgenic mice using specific keratin promoters. In this study, we analyzed female genital tract from our various transgenic mice, and finally we found that K5 E2F1 transgenic mice developed cancer of the uterine cervix. E2F1, as well as keratin 5, was overexpressed in the squamous epithelium of uterine cervix and cancer tissues from K5 E2F1 transgenic mice. In general, as requirements of an ideal adequate animal model of cancer, the tumors developing in such a model must display a reasonable degree of similarity with human cancer. Cervical cancers from K5 E2F1 transgenic mice were similar to human cervical cancers as follows: i)They were squamous cell carcinomas. ii)They developed from similar precursor lesions, cervical intraepithelial neoplasias (CINs). iii)They were metastasizing to pelvic lymph nodes.These data suggest that K5 E2F1 transgenic mice appear to be an exellent animal model for analysis of carcinogenesis of uterine cervix. Less