Antiestrogens activate an estrogen receptor mutant exhibiting enhanced binding to the estrogen response element.
The appearance of constitutively active and antiestrogen resistant estrogen receptor variants has been proposed as one of several factors leading to the development of antiestrogen resistant breast cancers. We recently described the ER2, estrogen receptor mutant, which exhibits enhanced binding to the estrogen response element on DNA, and partial constitutive estrogen-independent) ability to activate transcription. In this work we used transient transfections to show that the antiestrogens trans hydroxytamoxifen and ICI 164,384 are unable to suppress the constitutive activity of the ER2 mutant. Instead, both antiestrogens were concentration-dependent activators of the ER2 mutant. The ER2 mutant appears to be the first estrogen receptor mutant to show activation of a simple estrogen response element-containing promoter using the "pure" antiestrogen ICI 164,384.
Xing
H
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Department of Biochemistry, University of Illinois, Urbana 61801.
Haase
S
S
Shapiro
D J
DJ
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004351:Drug Resistance; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008099:Liver; D009154:Mutation; D053284:Polyunsaturated Alkamides; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014981:Xenopus
D004965:Estrogen Antagonists; D053284:Polyunsaturated Alkamides; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol; C051781:ICI 164384; D004247:DNA