OVARY - B
Tuesday, August 3, 2004
10:30 AM–12:30 PM
(461) EFFECT OF EPIDERMAL GROWTH FACTOR ON THE EXPRESSION OF TWO FORMS OF PROGESTERONE RECEPTORS IN EPITHELIAL OVARIAN CANCER.
Park, Se-Hyung1, Choi, Kyung-Chul1, Kim, Ki-Yon1, Auersperg, Nelly1, Leung, Peter CK1, 1 Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada
ABSTRACT- Epidermal growth factor (EGF) and its receptor (EGFR) are reported to be present and implicated in the growth and progression of 33-75 % ovarian cancer. Ovarian cancers that express increased EGFR are associated with poor survival and EGF is shown to stimulate the growth of ovarian cancer cells in vitro. Progesterone (P4) and its receptor (PR) may reduce the risk of ovarian carcinoma induced by E2 during an estrogen replacement therapy. However, the molecular mechanism of the anticancer effect of P4 is not fully understood. Although crosstalk between growth factors and the estrogen receptor (ER) signaling pathway has been elucidated, the exact mechanism in the expression of progesterone receptor (PR) by EGF in ovarian cancer has not been elucidated. Thus, in the present study, we examined the role of EGF in the regulation of two forms of PRs, PRA and PRB. To examine the role of EGF, IOSE-80PC (a post-crisis line of immortalized ovarian surface epithelial cells) and ovarian cancer cell lines, OVCAR-3 and SKOV-3, were treated with EGF in a dose-dependent manner, and thymidine incorporation assay was performed. EGFR mRNA and protein are constitutively expressed in these cell lines. Treatment with EGF for 24 h resulted in the stimulation of cell proliferation in IOSE-80PC and ovarian cancer cell lines. To further examine the effect of EGF on the expression of PRA and PRB, RT-PCR and immunoblot analyses were performed in OVCAR-3 cells following treatment with EGF. Increasing doses of EGF (0.1 to 10 ng/ml) increased PRA mRNA and decreased PRB mRNA in a dose dependent manner. In parallel with its mRNA level, the expression level of PR-A protein, but not PR-B, was increased by EGF treatment in a dose-dependent manner in these cells. These results suggest that EGF may affect progesterone signaling through the modulation of expression of progesterone receptors at the transcriptional and translational levels in ovarian cancer cells. [This work was supported by the Canadian Institutes of Health Research.]
KEY WORDS: EGF, Gene expression, Ovarian cancer, P4, PR