Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites.
The transactivation properties of the two estrogen receptors, ERalpha and ERbeta, were examined with different ligands in the context of an estrogen response element and an AP1 element. ERalpha and ERbeta were shown to signal in opposite ways when complexed with the natural hormone estradiol from an AP1 site: with ERalpha, 17beta-estradiol activated transcription, whereas with ERbeta, 17beta-estradiol inhibited transcription. Moreover, the antiestrogens tamoxifen, raloxifene, and Imperial Chemical Industries 164384 were potent transcriptional activators with ERbeta at an AP1 site. Thus, the two ERs signal in different ways depending on ligand and response element. This suggests that ERalpha and ERbeta may play different roles in gene regulation.
Paech
K
K
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143-0446, USA.
Webb
P
P
Kuiper
G G
GG
Nilsson
S
S
Gustafsson
J
J
Kushner
P J
PJ
Scanlan
T S
TS
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D002460:Cell Line; D004054:Diethylstilbestrol / Q000378:metabolism / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D020849:Raloxifene Hydrochloride; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D013629:Tamoxifen / Q000378:metabolism / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000378:metabolism
D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D008024:Ligands; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011960:Receptors, Estrogen; D018808:Transcription Factor AP-1; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D004054:Diethylstilbestrol; C051781:ICI 164384