Estrogen and aryl hydrocarbon receptor expression and crosstalk in human Ishikawa endometrial cancer cells

J Steroid Biochem Mol Biol. 2000 Apr;72(5):197-207. doi: 10.1016/s0960-0760(00)00030-3.

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

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Benzo(a)pyrene / pharmacology
  • Benzofurans / pharmacology
  • Chloramphenicol O-Acetyltransferase / drug effects
  • Chloramphenicol O-Acetyltransferase / genetics
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Cytochrome P-450 CYP1A1 / drug effects
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A1 / metabolism
  • DNA-Binding Proteins*
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism*
  • Estradiol / pharmacology
  • Female
  • Humans
  • Polychlorinated Dibenzodioxins / pharmacology
  • Promoter Regions, Genetic
  • Receptors, Aryl Hydrocarbon / agonists
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Receptors, Estrogen / drug effects
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / drug effects
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism
  • Transcription Factors / drug effects
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Tumor Cells, Cultured

Substances

  • ARNT protein, human
  • Benzofurans
  • DNA-Binding Proteins
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Transcription Factors
  • 6-methyl-1,3,8-trichlorodibenzofuran
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Benzo(a)pyrene
  • Estradiol
  • Cytochrome P-450 CYP1A1
  • Chloramphenicol O-Acetyltransferase