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• W2000930609 abstract "Retinoic acid receptor α1 (RARα1) gene expression is induced by 17β-estradiol (E2) in estrogen receptor (ER)-positive breast cancer cells, and the −100 to −49 region of the RARα1 gene promoter was previously shown to be required for E2-responsiveness. This region of the RARα1 promoter was further analyzed using the following oligonucleotides: −100 to −49 (RAR4); −79 to −56 (RAR3); −79 to −49 (RAR2); −100 to −58 (RAR1); and their derived promoter reporter constructs (pRAR4, pRAR3, pRAR2, and pRAR1). In transient transfection studies in MCF-7 human breast cancer cells, pRAR2 and pRAR1 were E2-responsive; both of the RARα1 gene promoter inserts contained two GC-rich sites and bound Sp1 protein in gel mobility shift assays. Using wild-type[ 32P]RAR2 and oligonucleotides mutated in one or both GC-rich sites, it was shown that ER enhanced Sp1 binding to both sites, but a ternary ER-Sp1-DNA complex was not observed in gel mobility shift assays. In transient transfection assays, each of the GC-rich motifs were sufficient for E2-induced transactivation. In ER-negative MDA-MB-231 cells transiently transfected with pRAR2, E2 responsiveness was observed only in cells cotransfected with wild-type ER or 11C-ER containing a deletion of the DNA-binding domain but not with ER variants that express activation function-1 (AF-1) or AF-2. Using a similar approach, it was shown that the GC-rich sites in RAR1 were also sufficient for ER activation. These results demonstrate that interaction of a transcriptionally active ER/Sp1 complex with GC-rich motifs is required for hormone inducibility of the downstream region of the RARα1 gene promoter." @default.
• W2000930609 created "2016-06-24" @default.
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• W2000930609 date "1998-06-01" @default.
• W2000930609 modified "2023-10-03" @default.
• W2000930609 title "Estrogen-Induced Retinoic Acid Receptor α1 Gene Expression: Role of Estrogen Receptor-Sp1 Complex" @default.
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• W2000930609 doi "https://doi.org/10.1210/mend.12.6.0125" @default.
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