Development of Animal Models (Transgenic Mice) for Ovarian Cancer

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The mortality rate of ovarian cancer in Japan is increasing year by year, and more than 8 times in these 50 years. It is difficult to diagnose ovarian cancer in early stage, because patients with ovarian cancer have no symptoms or just mild symptoms until the disease is in an advanced stage such as stage III/IV and hard to treat. Therefore, ovarian cancer is sometimes called the "silent killer."Recently, we have established a lot of transgenic mice overexpressing various growth factors or oncogenes, such as TGF-α, c-src, c-erbB2, IGF-1, and E2F1, using specific keratin promoters. These transgenic mice developed various epithelial tomors including skin, prostate, gallbladder and uterine cervix. In these transgenic mice, keratin 1, 5, 14 and loricrin were used as promoters. However, there is no possibilities that these mice were associated with ovarian tumorigenesis, because these promoters of transgenic mice were not expressed in ovarian surface epithelium (OSE).In this study, we aimed at development of animal models for ovarian cancer. First, we explored the promising candidate molecules as a specific promoter for making transgenic mice associated with ovarian tumorigenesis, and found that keratin 8 (K8) was specifically expressed in ovarian surface epithelium. Next, we made K8,GFP (green fluorescent protein) transgenic mice to confirm the distribution and localization of K8 expression. Finally, we attempted to make some transgenic mice, K8.IGF-1 transgenic mice, K8.E2F1 transgenic mice, K8.erbB2 transgenic mice, and K8.src transgenic mice. However these projects are still on going, our preliminary data showed that papillary proliferation of OSE, considered as precursor lesions of ovarian dancer, was observed in erbB2 transgenic mice.