| Title | IN VIVO PROFILING OF ESTROGEN RECEPTOR/SPECIFICITY PROTEIN-DEPENDENT TRANSACTIVATION. | | Author(s) | Wu F, Xu R, Martin J, Safe S | | Institution | Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843 USA; Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, TX 77030-3303 USA; Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466 USA. | | Source | Endocrinology 2008 Jul 17. | | Abstract | 17beta-Estradiol (E2) activates the estrogen receptor (ER) through multiple genomic and non-genomic pathways in various tissues/organs. ERalpha/Sp-dependent activation of E2-responsive genes containing GC-rich promoters has been identified in breast and other cancer cell lines and in this study, we describe transgenic animals overexpressing a transgene containing three tandem GC-rich sites linked to a minimal TATA or thymidine kinase (TK) promoter and a luciferase gene. Several mouse lines expressing the transgenes were characterized and, in line #15, E2 induced a 9-fold increase in luciferase activity in the female mouse uterus and the synthetic estrogens bisphenol A (BPA) and nonylphenol (NP) also induced uterine luciferase activity. The "pure" antiestrogen ICI 182,780 induced luciferase activity in the mouse uterus and similar results were observed for ICI 182,780 in breast cancer cells transfected with this construct. Difference in the ER agonist and antagonist activities of E2, NP, BPA and ICI 182,780 were investigated in the male testis and penis and the male and female stomach in line #15 transgenic mice. All of these tissues were hormone-responsive however the patterns of induced or repressed luciferase activity were ligand structure-, tissue- and sex-dependent. These results demonstrate for the first time hormonal activation or repression of a GC-rich promoter in vivo and the results suggest that the ERalpha/Sp pathway may contribute to E2-dependent induction and repression of genes. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18635651 |
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