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[Cancer Research 63, 1389-1397, March 15, 2003]
© 2003 American Association for Cancer Research

Tumor Biology

Female Mice Chimeric for Expression of the Simian Virus 40 TAg under Control of the MISIIR Promoter Develop Epithelial Ovarian Cancer1

Denise C. Connolly2, Rudi Bao3, Alexander Yu Nikitin, Kasie C. Stephens, Timothy W. Poole4, Xiang Hua, Skye S. Harris, Barbara C. Vanderhyden and Thomas C. Hamilton

Ovarian Cancer Program [D. C. C., R. B., K. C. S., T. W. P., S. S. H., T. C. H.] and Transgenic Mouse Facility [X. H.], Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111; Department of Biomedical Sciences, Cornell University, Ithaca, New York, 14853 [A. Y. N.]; and Departments of Cellular and Molecular Medicine, and Obstetrics and Gynecology, University of Ottawa, and Ottawa Regional Cancer Centre, Ottawa, Ontario K1H 1C4, Canada [B. C. V.]

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 geneticmouse 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 Mullerian inhibitory substance type II receptor gene promoter develop bilateral 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 cytokeratins 8 and 19, and the absence of {alpha}-inhibin, a protein characteristically 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 advance our understanding of this neoplasm, and serve as a useful tool for the evaluation of emerging detection and treatment strategies.




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