Abstract
Ishikawa endometrial cancer cells express the estrogen receptor (ER), and this study investigates aryl hydrocarbon receptor (AhR) expression and inhibitory AhR-ER crosstalk in this cell line. Treatment of Ishikawa cells with the AhR agonist [3H]2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) gave a radiolabeled nuclear complex that sedimented at 6.0 S in sucrose density gradients, and Western blot analysis confirmed that Ishikawa cells expressed human AhR and AhR nuclear translocator (Arnt) proteins. Treatment of Ishikawa cells with 10 nM TCDD induced a 9.7-fold increase in CYP1A1-dependent ethoxyresorufin O-deethylase (EROD) activity and a 10.5-fold increase in chloramphenicol acetyltransferase (CAT) activity in cells transfected with pRNH11c containing an Ah-responsive human CYP1A1 gene promoter insert (-1142 to +2434). Inhibitory AhR-ER crosstalk was investigated in Ishikawa cells using E2-induced cell proliferation and transcriptional activation assays in cells transfected with E2-responsive constructs containing promoter inserts from the progesterone receptor and vitellogenin A2 genes. AhR agonists including TCDD, benzo[a]pyrene (BaP) and 6-methyl-1,3,8-trichlorodibenzofuran, inhibited 32-47% of the E2-induced responses. In contrast, neither estrogen nor progesterone inhibited EROD activity induced by TCDD in Ishikawa cells, whereas inhibitory ER-AhR crosstalk was observed in ECC-1 endometrial cells suggesting that these interactions were cell context-dependent.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma / drug therapy
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Adenocarcinoma / genetics
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Adenocarcinoma / metabolism*
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Aryl Hydrocarbon Receptor Nuclear Translocator
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Benzo(a)pyrene / pharmacology
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Benzofurans / pharmacology
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Chloramphenicol O-Acetyltransferase / drug effects
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Chloramphenicol O-Acetyltransferase / genetics
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Chloramphenicol O-Acetyltransferase / metabolism
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Cytochrome P-450 CYP1A1 / drug effects
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Cytochrome P-450 CYP1A1 / genetics
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Cytochrome P-450 CYP1A1 / metabolism
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DNA-Binding Proteins*
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Endometrial Neoplasms / drug therapy
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Endometrial Neoplasms / genetics
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Endometrial Neoplasms / metabolism*
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Estradiol / pharmacology
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Female
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Humans
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Polychlorinated Dibenzodioxins / pharmacology
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Promoter Regions, Genetic
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Receptors, Aryl Hydrocarbon / agonists
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Receptors, Aryl Hydrocarbon / genetics
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Receptors, Aryl Hydrocarbon / metabolism*
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Receptors, Estrogen / drug effects
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Receptors, Estrogen / genetics
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Receptors, Estrogen / metabolism*
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Receptors, Progesterone / drug effects
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Receptors, Progesterone / genetics
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Receptors, Progesterone / metabolism
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Transcription Factors / drug effects
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Transcription Factors / metabolism
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Transcription, Genetic
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Tumor Cells, Cultured
Substances
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ARNT protein, human
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Benzofurans
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DNA-Binding Proteins
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Polychlorinated Dibenzodioxins
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Receptors, Aryl Hydrocarbon
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Receptors, Estrogen
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Receptors, Progesterone
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Transcription Factors
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6-methyl-1,3,8-trichlorodibenzofuran
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Aryl Hydrocarbon Receptor Nuclear Translocator
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Benzo(a)pyrene
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Estradiol
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Cytochrome P-450 CYP1A1
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Chloramphenicol O-Acetyltransferase