Inhibition of estrogen-induced progesterone receptor in MCF-7 human breast cancer cells by aryl hydrocarbon (Ah) receptor agonists.
17 beta-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-1,3,8-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.[1]References
- Inhibition of estrogen-induced progesterone receptor in MCF-7 human breast cancer cells by aryl hydrocarbon (Ah) receptor agonists. Harper, N., Wang, X., Liu, H., Safe, S. Mol. Cell. Endocrinol. (1994) [Pubmed]
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