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

“高风险”人乳头瘤病毒（hpv），如HPV-16和18，在80-90%的宫颈浸润性癌症中发现。然而，hpv感染似乎不足以致癌，因为人类宫颈鳞状上皮中含有高危hpv的大多数病变不会进展为浸润性癌。此外，一些研究人员报道，HPV或E6/E7转基因小鼠发生宫颈上皮内瘤变，但未发生浸润性癌症。这些证据表明，除了hpv感染外，其他遗传改变可能对宫颈癌的发生也很重要。近年来，我们建立了许多使用特异性角蛋白启动子的转基因小鼠，这些小鼠发生了包括皮肤、前列腺和胆囊在内的各种上皮肿瘤。在我们最近的研究中，子宫颈鳞状上皮表达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，使用特异性角蛋白启动子的转基因小鼠子宫颈中可能有更多的靶蛋白过表达。在本研究中，我们对各种转基因小鼠的雌性生殖道进行了分析，最终发现K5 E2F1转基因小鼠发生子宫颈癌。在K5 E2F1转基因小鼠的子宫颈鳞状上皮和癌组织中，E2F1和角蛋白5均过表达。一般来说，作为理想的足够的癌症动物模型的要求，在这种模型中发展的肿瘤必须与人类癌症具有合理程度的相似性。K5 E2F1转基因小鼠的宫颈癌与人宫颈癌有以下相似之处：1)均为鳞状细胞癌。ii)它们起源于相似的前体病变，即宫颈上皮内瘤变（CINs）。iii)转移到盆腔淋巴结。这些数据表明，K5 E2F1转基因小鼠可能是分析子宫颈癌变的良好动物模型。少

项目成果

Targeted expression of c-Src in epidermal basal cells leads to enhanced skin tumor promotion, malignant progression, and metastasis.

• 发表时间: 2003-08
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Takashi Matsumoto;Jianghong Jiang;K. Kiguchi;L. Ruffino;S. Carbajal;L. Beltrán;D. Bol;M. P. Rosenberg;J. DiGiovanni

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

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。

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

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。