Cell Lines Hydrocarbon Responsiveness in Human Ovarian Carcinoma Characterization of the Aryl Hydrocarbon Receptor and Aryl

The human ovarian carcinoma cell lines PE01, PE04, and PE06 express the estrogen receptor and studies with the PE04 cells have shown that tamoxifen inhibits 17ß-estradiol-induced proliferation. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a broad spectrum antiestrogen which works through the aryl hydrocarbon receptor. Incubation of the three cell lines with | 'II11 ( 1)1) followed by isolation of nuclear extracts showed that the PE01, PE04, and PE06 cells express the aryl hydrocarbon receptor (23 to 87 fmol/mg protein) which exhibits sedimentation properties (7.5 to 7.9 S) on sucrose gradients similar to that observed in other mammalian species. Aryl hydrocarbon responsiveness was determined by the induction of P4501A1 inKNA levels and ethoxyresorufin O-deethylase activity by TCDD. Induction of both parameters was observed only in the PE04 cells. Gel mobility shift assays with a consensus dioxin-responsive element (DRE, 26-mer) showed that after incubation of the nuclear extracts from the 3 cell lines with 32P-DRE a retarded band formed only with nuclear receptor complex from PE04 cells. 17ß-Estradiol stimulated proliferation of the l'I 04 and PE06 but not the PE01 cells; 1 MMTCDD alone either did not affect or inhibited the growth of these cells and 1 IIMTCDD signifi cantly inhibited the 17/3-estradiol-induced proliferation of the PE04 and PE06 cells. Treatment of the PE04 cells with l IIM17ß-estradiol resulted in a time-dependent enhanced secretion of the A/, 52,000 protein (procathepsin D) and, after 48 h, a 51 % increase in the secretion of this protein was observed. Colreatment of the PE04 cells with 0.1 or 1.0 nm TCDD com pletely inhibited the 17ß-estradiol-induced secretion of the AÕ,52,000 protein. These data show that TCDD exhibits antiestrogenic activity in estrogen receptor-positive ovarian carcinoma cell lines; however, in the PE06 cells, there was no correlation between the effects of TCDD on the induction of CYPIAI gene expression and the results of the gel shift assay (i.e., nonresponsiveness) versus the observed antiestrogenic activity.