TY - JOUR
T1 - Ligand structure-dependent activation of estrogen receptor α/Sp by estrogens and xenoestrogens
AU - Wu, Fei
AU - Khan, Shaheen
AU - Wu, Qian
AU - Barhoumi, Rola
AU - Burghardt, Robert
AU - Safe, Stephen
N1 - Funding Information:
The financial assistance of the National Institutes of Health (ES04917, CA104116 and ES09106) and the Texas Agricultural Experiment Station is gratefully acknowledged.
PY - 2008/5
Y1 - 2008/5
N2 - 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.
AB - 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.
KW - 17β-Estradiol
KW - Antiestrogens
KW - ERα/Sp
KW - Transactivation
KW - Xenoestrogens
UR - http://www.scopus.com/inward/record.url?scp=44649148892&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44649148892&partnerID=8YFLogxK
U2 - 10.1016/j.jsbmb.2008.02.008
DO - 10.1016/j.jsbmb.2008.02.008
M3 - Article
C2 - 18400491
AN - SCOPUS:44649148892
SN - 0960-0760
VL - 110
SP - 104
EP - 115
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
IS - 1-2
ER -