The Role of a First Intron Negative Regulatory Element in the Repression of EGFR Expression in Hormone-Dependent Breast Cancer
Abstract
Breast cancer progression from a hormone-dependent, anti-estrogen sensitive to a hormone-independent, anti- estrogen insensitive phenotype involves the loss of estrogen receptor (ER) expression and the up-regulation of a number of growth factor receptors and/or their ligands, including the epidermal growth factor receptor (EGFR). EGFR is overexpressed in breast cancer and is inversely correlated with ER status in a majority of breast tumors. EGFR overexpression is associated with a more aggressive phenotype and predicts for poor response to endocrine therapy, suggesting up-regulation of EGFR is involved in the progression to a more aggressive, hormone-independent phenotype. Results indicate that a 96bp fragment within the EGFR gene first intron repressed EGFR gene expression in ER+ breast cancer cells. Furthermore, the 96bp intron element demonstrated differential factor binding in ER+ vs. ER- breast cancer cells. Results point to the 96bp intron element as being the optimal repressor element. Disruption of this element and/or the factors with which it interacts results in the abolishment of transcriptional repression. Moreover, it appears that the 96bp element interacts with a cell-specific factor, as well as a factor that is estrogen-regulated. Tanscriptional repression plays a major role in the regulation of EGFR gene expression in hormone-dependent breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADB266031
Entities
People
- Melissa Wilson
Organizations
- Georgetown University