Ligand structure-dependent activation of estrogen receptor α/Sp by estrogens and xenoestrogens

Fei Wu, Shaheen Khan, Qian Wu, Rola Barhoumi, Robert Burghardt, Stephen Safe

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

This study investigated the effects of E2, diethylstilbestrol (DES), antiestrogens, the phytoestrogen resveratrol, and the xenoestrogens octylphenol (OP), nonylphenol (NP), endosulfan, kepone, 2,3,4,5-tetrachlorobiphenyl-4-ol (HO-PCB-Cl4), bisphenol-A (BPA), and 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) on induction of luciferase activity in breast cancer cells transfected with a construct (pSp13) containing three tandem GC-rich Sp binding sites linked to luciferase and wild-type or variant ERα. The results showed that induction of luciferase activity was highly structure-dependent in both MCF-7 and MDA-MB-231 cells. Moreover, RNA interference assays using small inhibitory RNAs for Sp1, Sp3 and Sp4 also demonstrated structure-dependent differences in activation of ERα/Sp1, ERα/Sp3 and ERα/Sp4. These results demonstrate for the first time that various structural classes of ER ligands differentially activate wild-type and variant ERα/Sp-dependent transactivation, selectively use different Sp proteins, and exhibit selective ER modulator (SERM)-like activity.

Original languageEnglish (US)
Pages (from-to)104-115
Number of pages12
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume110
Issue number1-2
DOIs
StatePublished - May 1 2008

Keywords

  • 17β-Estradiol
  • Antiestrogens
  • ERα/Sp
  • Transactivation
  • Xenoestrogens

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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