The PI's laboratory has recently discovered a novel, soluble truncated form of the receptor encoded by the proto-oncogene c-erbBI.(1-2) Preliminary data from the PI's laboratory and others suggest that the related proto-oncogenes, c-erbB2 and c-erbB3, also encode soluble receptor forms. (3-6) The c-erbB family of proto-oncogenes has been implicated in the development of both breast and ovarian carcinomas. In this application, we hypothesize that soluble forms of receptors encoded by the c-erbB family of proto-oncogenes may be important in ovarian carcinogenesis and mav have clinical utility as markers of disease activity, as prognostic indicators, and/or as potential targets for future therapeutic approaches. To test this hypothesis we propose to measure the serum levels of soluble forms of c-erbB receptors in a large cohort of women with advanced ovarian cancer. We will compare the expression of soluble receptors in serum with c-erbB expression in tumor cells as determined by immunohistochemical analysis. We will then compare c-erbB patterns of expression (in sera and tumor samples) with established histologic and clinical parameters. We also propose to delineate the molecular basis for the synthesis of soluble c-erbB receptor forms in ovarian tumors, and will test the ability of these soluble receptors to inhibit ovarian carcinoma cell growth in vitro.
