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

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-Cl(4)), 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 (pSp1(3)) containing three tandem GC-rich Sp binding sites linked to luciferase and wild-type or variant ERalpha. 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 ERalpha/Sp1, ERalpha/Sp3 and ERalpha/Sp4. These results demonstrate for the first time that various structural classes of ER ligands differentially activate wild-type and variant ERalpha/Sp-dependent transactivation, selectively use different Sp proteins, and exhibit selective ER modulator (SERM)-like activity.

• Authors: Fei Wu, Shaheen Khan, Qian Wu, Rola Barhoumi, Robert Burghardt, Stephen Safe
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 110 Issue 1-2 Pg. 104-15 (May 2008) ISSN: 0960-0760 [Print] England
• PMID: 18400491 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Benzhydryl Compounds
• Estrogen Receptor Modulators
• Estrogen Receptor alpha
• Estrogens
• Phenols
• Phytoestrogens
• Sp1 Transcription Factor
• Sp4 Transcription Factor
• Stilbenes
• octylphenol
• Sp3 Transcription Factor
• Estradiol
• Diethylstilbestrol
• nonylphenol
• bisphenol A
• Resveratrol
• Chlordecone

Topics

• Benzhydryl Compounds
• Blotting, Western
• Cell Line, Tumor
• Chlordecone (pharmacology)
• Diethylstilbestrol (pharmacology)
• Estradiol (pharmacology)
• Estrogen Receptor Modulators (pharmacology)
• Estrogen Receptor alpha (agonists, genetics, metabolism)
• Estrogens (pharmacology)
• Fluorescence Resonance Energy Transfer
• Humans
• Phenols (pharmacology)
• Phytoestrogens (pharmacology)
• RNA Interference
• Resveratrol
• Reverse Transcriptase Polymerase Chain Reaction
• Sp1 Transcription Factor (agonists, genetics, metabolism)
• Sp3 Transcription Factor (agonists, genetics, metabolism)
• Sp4 Transcription Factor (agonists, genetics, metabolism)
• Stilbenes (pharmacology)
• Transfection