TRUNCATED C-ERBB RECEPTORS IN WOMEN WITH OVARIAN CANCER

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.