Inhibition of estrogen-induced progesterone receptor in MCF-7 human breast cancer cells by aryl hydrocarbon (Ah) receptor agonists

N. Harper, X. Wang, H. Liu, S. Safe

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

17β-Estradiol (E2) induces progesterone receptor (PR) binding, immunoreactive protein, nuclear PR formation and PR mRNA levels in MCF-7 human breast cancer cells. Gel mobility shift analysis of nuclear extracts from E2-treated cells also exhibited a higher intensity retarded band associated with formation of a PR complex with a consensus [32P]progesterone/glucocorticoid responsive element. In contrast, 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alone did not alter or decrease these same responses in MCF-7 cells; however, in cells co-treated with 1 nM TCDD plus 1 nM E2, TCDD significantly inhibited all the E2-induced responses. Scatchard analysis of PR binding demonstrated that TCDD decreased the number of E2-induced PR cellular binding sites but not the binding affinity of the PR for a radiolabeled promegestrone. In parallel studies, 3-methylcholanthrene, a prototypical polynuclear aromatic hydrocarbon, also inhibited E2-induced PR binding and immunoreactive protein. For a series of halogenated aromatics including 2,3,7,8- and 1,2,7,8-tetrachlorodibenzofuran, 1,3,7,8-TCDD and 6-methyl-l,3,8-trichlorodibenzofuran, their rank order potency for inhibiting E2-induced PR binding paralleled their rank order binding to the aryl hydrocarbon (Ah) receptor. These results support a role for the Ah receptor in mediating the antiestrogenic activity of polynuclear and halogenated aromatic hydrocarbons and illustrate cross-talk between the Ah and estrogen receptor signal transduction pathways.

Original languageEnglish (US)
Pages (from-to)47-55
Number of pages9
JournalMolecular and cellular endocrinology
Volume104
Issue number1
DOIs
StatePublished - Aug 1994

Keywords

  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin
  • Breast cancer cells
  • Inhibition
  • Progesterone receptor binding

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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