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 17β-estradiol-induced proliferation. 2,3,7,8-Tetrachlo-rodibenzo-p-dioxin (TCDD) is a broad spectrum antiestrogen which works through the aryl hydrocarbon receptor. Incubation of the three cell lines with [3H]TCDD 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 mRNA levels and ethoxyresorufln 0-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. 17β-Estradiol stimulated proliferation of the PE04 and PE06 but not the PE01 cells; 1 IIM TCDD alone either did not afreet or inhibited the growth of these cells and 1 nM TCDD significantly inhibited the 17β-estradiol-induced proliferation of the PE04 and PE06 cells. Treatment of the PE04 cells with 1 nM 17β-estradiol resulted in a time-dependent enhanced secretion of the Afr 52,000 protein (procathe-psin D) and, after 48 h, a 51 % increase in the secretion of this protein was observed. Cotreatment of the PE04 cells with 0.1 or 1.0 nM TCDD completely inhibited the 17β-estradiol-induced secretion of the Mr 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 CYP1A1 gene expression and the results of the gel shift assay (Le., nonresponsiveness) versus the observed antiestrogenic activity.
|Original language||English (US)|
|Number of pages||6|
|State||Published - Apr 1993|
ASJC Scopus subject areas
- Cancer Research