SELECTIVE-INHIBITION OF ESTROGEN-REGULATED GENE-EXPRESSION IN-VIVO BYTHE PURE ANTIESTROGEN ICI-182,780

Estrogen-stimulated cell proliferation is thought to be mediated by th e induction of growth-regulatory factors. Abnormal regulation of such factors may be associated with tumorigenesis. Two such factors, vascul ar endothelial growth factor and c-fos, are rapidly induced in the ute rus by estrogens. We show that the induction of these transcripts by 1 7 beta-estradiol or tamoxifen is selectively blocked by the pure antie strogen ICI 182,780 in a dose-dependent manner. This indicates that in duction of the two genes requires different Levels of estrogen recepto r or that their induction occurs by different mechanisms. This suggest s that selective dose-dependent antagonism of estrogen-dependent trans cription may be possible in target tissues and tumors.