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

K5 E2F1转基因小鼠子宫颈癌变机制分析

• 批准号: 15591755
• 负责人: MATSUMOTO Takashi
• 金额: $ 2.37万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591755/
• 关键词: Uterine cervical cancer; Animal model; Transgenic mice; E2F1; Tumorigenesis

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

在子宫宫颈的80-90％的侵入性癌症中，发现了“高风险”人乳头瘤病毒（HPV），例如HPV-16和-18。然而，HPV感染似乎不足以进行致癌，因为含有高风险HPV的人宫颈鳞状上皮中的大多数病变都不会发展为侵入性癌。此外，一些研究人员报告说，HPV或E6/E7转基因小鼠产生了颈椎内肿瘤，但没有侵入性癌症。这些证据表明，除HPV感染外，其他遗传改变对于宫颈癌也可能很重要。最近，我们使用特定的角蛋白启动子建立了许多转基因小鼠，这些小鼠开发了包括皮肤，前列腺和胆囊在内的各种上皮肿瘤。在我们最近的研究中，子宫颈子宫颈的鳞状上皮表达了K1，K5和K14，而Squaremo-Polumnar Junction的储备细胞具有K5的表达。这些结果表明，使用特定的角蛋白启动子在转基因小鼠的子宫宫颈中可能会过度表达靶标。在这项研究中，我们分析了各种转基因小鼠的雌性生殖道，最后发现K5 E2F1转基因小鼠患有子宫宫颈癌。 E2F1以及角蛋白5在子宫宫颈的鳞状上皮和来自K5 E2F1转基因小鼠的癌症组织中过表达。通常，作为理想适当动物模型的癌症模型的要求，在这种模型中发展的肿瘤必须表现出与人类癌症的合理程度。来自K5 E2F1转基因小鼠的宫颈癌与人类宫颈癌相似，如下所示：i）它们是鳞状细胞癌。 ii）他们从类似的前体病变，颈椎上皮肿瘤（CINS）发展。 iii）它们正在转移到骨盆淋巴结。这些数据表明，K5 E2F1转基因小鼠似乎是用于分析子宫宫颈癌发生的天生动物模型。较少的

项目成果

Tumor formation in mice with conditional inactivation of Brca1 in epithelial tissues

• DOI: 10.1038/sj.onc.1206825
• 发表时间: 2003-08-21
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Berton, TR;Matsumoto, T;Johnson, DG
• 通讯作者: Johnson, DG

Overexpression of c-src in epidermal basal cells of transgenic mice leads to enhanced skin tumor promotion, malignant progression, and metastasis

转基因小鼠表皮基底细胞中c-src的过度表达导致皮肤肿瘤的促进、恶性进展和转移增强

• 发表时间: 2003
• 期刊: Cancer Res 63
• 作者: Takashi Matsumoto;Jianghong Jiang;Kaoru Kiguchi;Lynnsie Ruffino;Steve Carbajal;Linda Beltran;David Bol;Michael P Rosenberg;John DiGiovanni
• 通讯作者: John DiGiovanni

Takashi Matsumoto et al.: "Targeted expression of c-src in epidermal basal cells leads to enhanced skin tumor promotion, malignant progression, and metastasis"Cancer Research. 63. 4819-4828 (2003)

Takashi Matsumoto 等人：“表皮基底细胞中 c-src 的靶向表达导致皮肤肿瘤促进、恶性进展和转移增强”癌症研究。

Development of transgenic mice that inducibly express an active form of c-src in the epidermis

• DOI: 10.1002/mc.20027
• 发表时间: 2004-08-01
• 期刊: MOLECULAR CARCINOGENESIS
• 影响因子: 4.6
• 作者: Matsumoto, T;Kiguchi, K;DiGiovanni, J
• 通讯作者: DiGiovanni, J

Thomas R Berton, Takashi Matsumoto et al.: "Tumor formation in mice with conditional inactivation of Brca1 in epithelial tissues"Oncogene. 22. 5415-5426 (2003)

Thomas R Berton、Takashi Matsumoto 等人：“上皮组织中 Brca1 条件性失活的小鼠肿瘤形成”癌基因。