the MISIIR Promoter Develop Epithelial Ovarian Cancer1

In women,>80 % of malignant ovarian tumors are of epithelial origin. Early detection of these tumors is very challenging, and extensive i.p. dissemination is common by the time of diagnosis. The lack of adequate genetic mouse models of ovarian carcinomas significantly delays advances in early detection and treatment. We report that female transgenic mice expressing the transforming region of SV40 under control of the Mul-lerian inhibitory substance type II receptor gene promoter develop bilat-eral ovarian tumors in 50 % of cases. Histologically, these tumors are poorly differentiated carcinomas with occasional cysts and papillary structures present at the surface of the ovary. These tumors disseminate i.p., invade omentum, and form ascites as do human ovarian carcinomas. The epithelial origin of these tumors is supported by detection of cyto-keratins 8 and 19, and the absence of -inhibin, a protein characteristi-cally expressed in normal granulosa cells and most granulosa cell tumors. Cell lines derived from the ascites exhibit the properties of epithelial ovarian cancer, such as anchorage-independent growth, tumorigenicity in immunocompromised mice, expression of epithelial cell markers, and organotropic implantation. The availability of a transgenic mouse model of disseminated ovarian carcinoma and respective cell lines should ad-vance our understanding of this neoplasm, and serve as a useful tool for the evaluation of emerging detection and treatment strategies