Selective inhibition of estrogen-regulated gene expression in vivo by the pure antiestrogen ICI 182,780.
Estrogen-stimulated cell proliferation is thought to be mediated by the induction of growth-regulatory factors. Abnormal regulation of such factors may be associated with tumorigenesis. Two such factors, vascular endothelial growth factor and c-fos, are rapidly induced in the uterus by estrogens. We show that the induction of these transcripts by 17beta-estradiol or tamoxifen is selectively blocked by the pure antiestrogen ICI 182,780 in a dose-dependent manner. This indicates that induction of the two genes requires different levels of estrogen receptor or that their induction occurs by different mechanisms. This suggests that selective dose-dependent antagonism of estrogen-dependent transcription may be possible in target tissues and tumors.
Hyder
S M
SM
Department of Integrative Biology, Pharmacology, and Physiology, University of Texas Health Sciences Center, Houston 77225, USA. shyder@farmr1.med.uth.tmc.edu
Chiappetta
C
C
Murthy
L
L
Stancel
G M
GM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation; D008222:Lymphokines / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D004965:Estrogen Antagonists; D004967:Estrogens; D008222:Lymphokines; D016760:Proto-Oncogene Proteins c-fos; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol