Estradiol Regulation of the Human Retinoic Acid Receptor α Gene in Human Breast Carcinoma Cells Is Mediated via an Imperfect Half-Palindromic Estrogen Response Element and Sp1 Motifs

摘要: Abstract Estrogen receptor (ER)-positive human breast carcinoma (HBC) cell lines express significantly higher levels of retinoic acid α (RARα) (isoform 1) mRNA than ER-negative HBCs. Estradiol enhances RARα expression in different ER-positive HBCs by 2–3-fold, which turn results increased sensitivity to the growth inhibitory effects acid. To investigate regulatory mechanisms estradiol-mediated enhancement expression, functional promoter for isoform 1 was cloned and used assess promoter-dependent firefly luciferase reporter gene activity transiently transfected (MCF-7 T47D) (MDA-MB-231) Deletional constructs were obtained further delineate region responsible activity. Here, we present evidence that approximately 130 bp fragment preceding transcriptional start site are hRAR expression. The is dependent on ER binding. Further deletional analysis showed a sequence 42 base pairs, located 100 bases upstream site, contains elements enhancement. Specific deletion either Sp1 motif or mutations imperfect half-palindromic estrogen response element this abolish its estradiol responsiveness transient transfections.