TRANSFECTION OF RAT OVARIAN SURFACE EPITHELIUM WITH ERB-B2 NEU INDUCES TRANSFORMED PHENOTYPES IN-VITRO AND THE TUMORIGENIC PHENOTYPE IN-VIVO/

The neu/c-erb-B2 gene is frequently amplified and/or overexpressed in human epithelial ovarian cancers. We have established an inbred animal model for ovarian cancer that mimics aspects of human ovarian cancer by transducing a spontaneously immortalized rat ovarian surface epithe lial cell line in culture with ecotropic retroviruses expressing a mut ated rat neu/ c-erb-B2 oncogene, Transfectants expressing neu at a hig h level exhibited altered morphology and behavior in two-dimensional a nd three-dimensional culture in Matrigel, could be cloned in soft agar , and were more invasive through a Matrigel membrane than control tran sfectants transduced with a similar retrovirus expressing the beta-gal actosidase gene, When injected intraperitoneally, neu-expressing trans fectants produced highly invasive, rapidly growing tumors that coated the peritoneal cavity and induced ascites formation, Furthermore, lieu transfectants could be grown as solid tumors when injected subepithel ially into the ovary. The neu-transfected cells also formed tumors whe n injected subcutaneously into the mammary fat pad, although they grew relatively poorly and often regressed, Transfectants expressing beta- galactosidase failed to produce tumors at any of the sites injected. A second rat ovarian surface epithelial cell line was similarly transdu ced with the neu/cerb-B2-expressing retrovirus, However, transformed p henotypes and tumorigenicity were not induced in this cell Line, These experiments show directly that overexpression of neu in an establishe d line of rat ovarian epithelium is extremely oncogenic, This animal m odel system may prove useful for the study of ovarian cancer biology i n immunocompetent animals.