Analysis of mechanism of carcinogenesis in uterine cervix of K5 E2F1 transgenic mice
| Project/Area Number |
15591755
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Ehime University |
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Principal Investigator |
MATSUMOTO Takashi Ehime University, School of Medicine, Instructor, 医学部, 助手 (20346670)
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| Co-Investigator(Kenkyū-buntansha) |
UEDA Norifumi Ehime University, School of Medicine, Professor, 医学部, 教授 (30030886)
ITO Masaharu Ehime University, School of Medicine, Professor, 医学部, 教授 (10136731)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Uterine cervical cancer / Animal model / Transgenic mice / E2F1 / Tumorigenesis |
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| Research Abstract |
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
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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
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Report
(3 results)
Research Products
(8 results)
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[Journal Article] Overexpression of c-src in epidermal basal cells of transgenic mice leads to enhanced skin tumor promotion, malignant progression, and metastasis2003
Author(s)
Takashi Matsumoto, Jianghong Jiang, Kaoru Kiguchi, Lynnsie Ruffino, Steve Carbajal, Linda Beltran, David Bol, Michael P Rosenberg, John DiGiovanni
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Journal Title
Cancer Res 63
Pages: 4819-4828
Description
「研究成果報告書概要(欧文)」より
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