Sp1 is essential for estrogen receptor alpha gene transcription

作者：deGraffenried LA; Hilsenbeck SG; Fuqua SAW^*

来源：Journal of Steroid Biochemistry and Molecular Biology, 2002, 82(1): 7-18.

DOI：10.1016/S0960-0760(02)00151-6

• estrogen receptor
• gene transcription
• linker-scanner mutation

The exact molecular mechanisms regulating estrogen receptor (ER)a 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 245 by of the 5'-flanking region of the gene. Three elements essential for full ERa promoter transcriptional activity were identified within the -245 to -192 by 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 Spa bind to this region using electrophoretic mobility shift assays. Exogenous expression of Sp1 or Spa in Sp1/3-negative Drosophila Schneider SL2 cells results in transactivation of the -245 to +212bp fragment of the ERa promoter. These data demonstrate that transcription of ERa is dependent upon the expression of members of the Spl family.

• 出版日期2002-9