Abstract: 7

HEPATOCYTE GROWTH FACTOR/SCATTER FACTOR AND ITS RECEPTOR c-MET IN CULTURED HUMAN OVARIAN SURFACE EPITHELIUM: INFLUENCE OF FAMILY HISTORY OF OVARIAN CANCER.

Alice S. T. Wong¹ , Peter C. K. Leung^{1 *}, Nelly Auersperg^{1 *}
Department of Obstetrics and Gynecology, The University of British Columbia, Vancouver, B. C., Canada ¹

Most ovarian cancers arise in the ovarian surface epithelium (OSE) that overlies the ovary. With neoplastic progression, OSE-derived carcinomas tend to acquire new, complex epithelial differentiation markers that are lacking in normal OSE. The interaction between hepatocyte growth factor/scatter factor (HGF/SF) and its receptor c-met is considered an important regulator of cell growth, motility and morphogenesis. Importantly for this study, inappropriate expression of HGF/SF-met induces the formation of cysts with enhanced epithelial differentiation which mimic preneoplastic ovarian lesions. In the present study, the expression of HGF/SF and c-met was compared by RT-PCR and Western blot in normal cultured OSE from 9 women with (FH-OSE) and 24 women with no (NFH-OSE) family histories of breast/ovarian cancer, and in 3 ovarian carcinoma lines. OSE cultures were also analyzed for cell growth in the presence of exogenous HGF/SF. Our data demonstrate that c-met is downregulated in prolonged cultures of NFH-OSE, but persists in FH-OSE and ovarian carcinomas. Thus, c-met correlates with other epithelial markers such as E-cadherin, which are enhanced and stabilized in neoplasia and, to a lesser degree, in FH-OSE. Exogenous HGF/SF was mitogenic in normal OSE. Interestingly, HGF/SF mRNA was detected in only 1 of 28 NFH-OSE cultures, but in 8 of 19 FH-OSE cultures and in 2 of 3 ovarian carcinoma lines, suggesting an autocrine regulatory interaction of HGF/SF-met in these cells. In analogy with the behavior in other cell types where an autocrine HGF/SF-met loop has been implicated in tumorigenic transformation, this change in FH-OSE may play a role in ovarian carcinogenesis. (Supported by N.C.I.Canada).

    This abstract is being presented on Sunday, August 1 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.