Study an ER Variant Identified from Breast Hyperplasis.
Abstract
We have isolated a variant form of the estrogen receptor (ER) from breast hyperplasias which displays a 100-fold increase in estrogen sensitivity. We have found this variant to be present in more than 20% of proliferative hyperplasias and also in the normal breast tissue adjacent to the hyperplasia. The research funded by this grant has focused on the function of this super-active ER variant in breast cancer, as well as the factors which regulate its expression in breast cancer cells as potential targets for clinical therapy. In transient transfection assays, the variant ER is activated by estrogen at much lower concentrations as compared to the wild-type, and forced expression of the ER variant in breast cancer cell lines increases cell proliferation. Expression of a variant ER which confers a proliferative advantage as well as a heightened sensitivity to estrogen might predispose breast hyperplasias to malignant progression. We are currently investigating the mechanism which confers this increased activity to the ER variant. Regulation of the expression of both the wild-type as well as the variant ER at the transcriptional level is also a potential target for clinical therapy. For this reason we have begun studies of the transcriptional factors which regulate activity of the ER gene promoter. Transient transfection studies in a panel of breast cancer cell lines indicate that the basal promoter of the ER 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, and the regulatory elements within this region are currently being investigated.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADA356206
Entities
People
- Linda A. Degraffenried
Organizations
- University of Texas Health Science Center at San Antonio