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

28 Citations (Scopus)

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

Fingerprint

Luciferases
Estrogen Receptors
Estrogens
Chemical activation
Ligands
Chlordecone
RNA
Endosulfan
Phytoestrogens
Diethylstilbestrol
Estrogen Receptor Modulators
Polychlorinated Biphenyls
RNA Interference
Modulators
Transcriptional Activation
Assays
Binding Sites
Cells
Breast Neoplasms
Proteins

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Ligand structure-dependent activation of estrogen receptor α/Sp by estrogens and xenoestrogens. / Wu, Fei; Khan, Shaheen; Wu, Qian; Barhoumi, Rola; Burghardt, Robert; Safe, Stephen.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 110, No. 1-2, 01.05.2008, p. 104-115.

Research output: Contribution to journalArticle

Wu, Fei ; Khan, Shaheen ; Wu, Qian ; Barhoumi, Rola ; Burghardt, Robert ; Safe, Stephen. / Ligand structure-dependent activation of estrogen receptor α/Sp by estrogens and xenoestrogens. In: Journal of Steroid Biochemistry and Molecular Biology. 2008 ; Vol. 110, No. 1-2. pp. 104-115.
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