Predoctoral Fellowship to Study an ER Variant Identified from Breast Hyperplasias.
Abstract
Studies have shown that elevated expression levels of estrogen receptor alpha (ERalpha) in benign breast epithelium is a risk factor for progression to invasive breast cancer. We have isolated a variant form of the ERalpha from breast hyperplasias which displays a 100-fold increase in estrogen sensitivity and increases cell proliferation. Expression of a variant ER that confers a proliferative advantage as well as a heightened sensitivity to estrogen might predispose breast hyperplasias to malignant progression. The research funded by this grant is focused on investigating the factors that regulate the expression of ERalpha and its variant's expression in breast cancer cells as potential targets for clinical therapy. We have previously shown that the basal promoter of the ERalpha gene lies within the first 245 bp of the 5' flanking region of the gene, and displays unusually high transcriptional activity in transient transfection assays. We now demonstrate that there are three elements within the ERalpha gene 5'flanking region that are critical for full promoter activity, and that the transcription factors Sp1 and Sp3 can each bind to this region, and are independently able to transactivate the ERalpha promoter. Inhibition of DNA binding by Sp1 to the ERalpha minimal promoter results in both a decrease of ERalpha promoter activity as well as ERalpha expression in breast cancer cells. We therefore conclude that Spl and/or Sp3 are critical for ERalpha expression in breast cancer cells, and are investigating other potential interacting factors in the regulation of ERalpha expression in breast cancer. The results of these experiments could prove clinically important in identifying new treatment targets.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA375244
Entities
People
- Linda A. Degraffenried
Organizations
- University of Texas Health Science Center at San Antonio