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 approximately 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.