title: Sp1 is essential for estrogen receptor alpha gene transcription.
abstract: The exact molecular mechanisms regulating estrogen receptor (ER)alpha expression in breast tumors are unclear, but studies suggest that the regulation is at least partly transcriptional. We therefore undertook a detailed analysis of ERalpha promoter activity in a number of breast cancer cell lines. We find that the majority of ERalpha promoter activity lies within the first 245bp of the 5'-flanking region of the gene. Three elements essential for full ERalpha promoter transcriptional activity were identified within the -245 to -192bp region in transient transactivation assays using linker-scanner mutation analysis. These three elements include two binding sites for the Sp1 family of transcription factors as well as a non-consensus E box. We show that both Sp1 and Sp3 bind to this region using electrophoretic mobility shift assays. Exogenous expression of Sp1 or Sp3 in Sp1/3-negative Drosophila Schneider SL2 cells results in transactivation of the -245 to +212bp fragment of the ERalpha promoter. These data demonstrate that transcription of ERalpha is dependent upon the expression of members of the Sp1 family.
authors.affiliation: Division of Medical Oncology, The University of Texas Health Science Center, San Antonio 78229, USA.
authors.forename: Linda A
authors.initials: LA
authors.lastname: deGraffenried
authors.forename: Susan G
authors.initials: SG
authors.lastname: Hilsenbeck
authors.forename: Suzanne A W
authors.initials: SA
authors.lastname: Fuqua
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000502:physiology; D004330:Drosophila; D024202:Electrophoretic Mobility Shift Assay; D047628:Estrogen Receptor alpha; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000502:physiology*; D051705:Sp3 Transcription Factor; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D051705:Sp3 Transcription Factor