Ligand structure-dependent activation of estrogen receptor alpha/Sp by estrogens and xenoestrogens.
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.
Wu
Fei
F
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, United States.
Khan
Shaheen
S
Wu
Qian
Q
Barhoumi
Rola
R
Burghardt
Robert
R
Safe
Stephen
S
D001559:Benzhydryl Compounds; D015153:Blotting, Western; D045744:Cell Line, Tumor; D007631:Chlordecone / Q000494:pharmacology; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D010636:Phenols / Q000494:pharmacology; D048789:Phytoestrogens / Q000494:pharmacology; D034622:RNA Interference; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D051705:Sp3 Transcription Factor / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D051706:Sp4 Transcription Factor / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology; D014162:Transfection; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D007631:Chlordecone; D004054:Diethylstilbestrol; D004958:Estradiol; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D004967:Estrogens; D010636:Phenols; D048789:Phytoestrogens; D000077185:Resveratrol; D016329:Sp1 Transcription Factor; D051705:Sp3 Transcription Factor; D051706:Sp4 Transcription Factor; D013267:Stilbenes; C474055:octylphenol; C025256:nonylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds