| Co-Investigator(Kenkyū-buntansha) |
UEDA Norifumi Ehime University, Graduate School of Medicine, Professor, 大学院医学研究科, 教授 (30030886)
ITO Masaharu Ehime University, Graduate School of Medicine, Professor, 大学院医学研究科, 教授 (10136731)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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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 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 result suggested that target gene s might be overexpressed in uterine cervix of transgenic mice using specific keratin promoters.
In this study, we analyzed female genital tract from our various mice, and finally we found that BK5.src^<wt> transgenic mice developed cancer of the uterine cervix. c-Src, as well as keratin 5, was overexpressed in the squamous epithelium of uterine cervix and cancer tissues from BK5.src^<wt> transgenic mice. Hyperplasia of uterine cervical epithelium was observed in a significant number of BK5.src^<wt> transgenic mice (18/20, 90%). The incidence of cervical intraepithelial neoplasias (CINs) was 30% (6/20) in BK5.src^<wt> transgenic mice. Invasive carcinoma was not observed. These findings suggest that constitutive expression of c-src in epithelium of uterine cervix may play an important role in tumorigenesis in this tissue.
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