Training in Support of a Research Project Entitled Study an ER Variant Identified from Breast Hyperplasis""

Abstract

Abstract : Studies have shown that elevated expression levels of estrogen receptor a (ER alpha) in benign breast epithelium is a risk factor for progression to invasive breast cancer, and that breast tumor tissue expresses elevated levels of ER alpha as compared to adjacent normal tissue. Previous studies suggest that ER expression is partly regulated at the transcriptional level. The research funded by this grant has focused on investigating the factors that regulate the expression of ER alpha in breast cancer cells as potential targets for clinical therapy. The ER alpha minimal promoter is contained within the -245 bp to +212 bp region of the gene, and contains an E box, a UC box, and a CA rich region that are critical for ER alpha promoter activity. A multi-protein complex containing Spl/Sp3, ER alpha and USF-l interacts with the ER alpha minimal promoter. Independently, Sp1 and USF-1 are able to each transactivate the ER alpha minimal promoter, but together have an additive, if not synergistic, effect on transactivation. Additionally, a short sequence (AACT) located at -203 bp to -200 bp appears to be essential for functional activity since mutation of these nucleotides results in loss of all transcriptional activity of the promoter. The results of these experiments could prove clinically important in identifying new treatment targets.