title: Transcriptional activation of cathepsin D gene expression by 17beta-estradiol: mechanism of aryl hydrocarbon receptor-mediated inhibition.
abstract: 17beta-estradiol (E2) induces cathepsin D gene expression in MCF-7 human breast cancer cells and this response is inhibited by aryl hydrocarbon receptor (AhR) agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Analysis of the cathepsin D gene promoter initially identified a pentanucleotide GCGTG core dioxin responsive element (DRE) that blocked E2 action by inhibiting formation of a transcriptionally active estrogen receptor (ER)-Sp1 complex. A second functional downstream inhibitory DRE (iDRE2) (-130 to -126) has now been identified in the cathepsin D gene promoter and inhibition of E2-induced transactivation involves inhibitory AhR crosstalk with the E2-responsive adenovirus major late promoter element (MLPE) at -124 to -104 in the cathepsin D gene promoter. The MLPE site primarily binds USF1/USF2 and ERalpha, and gel mobility shift and DNA footprinting assays show that the AhR complex decreases binding of these transcription factors to the MLPE.
authors.affiliation: Department of Veterinary Physiology and Pharmacology, Texas A & M University, College Station, TX 77843-4466, USA.
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.forename: I
authors.initials: I
authors.lastname: Samudio
authors.forename: S
authors.initials: S
authors.lastname: Safe
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology; D002402:Cathepsin D / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000378:metabolism; D020218:Response Elements; D015533:Transcriptional Activation / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D004958:Estradiol; D002402:Cathepsin D