Identification of Surrogate Markers for Estrogen Receptor Action in Breast Cancer Cells.
Annual rept. 1 Jul 97-30 Jun 98
DUKE UNIV DURHAM NC
Pagination or Media Count:
The human estrogen receptor ER is a ligand-inducible transcription factor that mediates the biological effects of the steroid hormone estrogen. Different ER ligands can regulate the expression of specific subsets of genes. While pure antiestrogens like ICI antagonize ER activity in all contexts, other antiestrogens such as tamoxifen can act as partial agonists in some situations and antagonists in others. Recently a second estrogen receptor ERb has been identified, and I have shown that this receptor is less sensitive to estrogen and antiestrogens. While both receptors are expressed in human breast tumors, I have been interested in identifying novel ER genomic targets, and studying their differential regulation by both ERs during the administration of agonists and antagonists. Using differential display PCR, I identified the hMIP gene human mitochondrial intermediate peptidase based on its upregulation by both ER agonists and antagonists. My current studies are aimed at further characterizing the ER regulation of hMIP. Furthermore, I have expanded my studies to include a dissection of the mechanism by which ERa and ERb show differential sensitivities to hormones so that we can better understand the regulation of our novel ER-regulated genes in the breast.
- Medicine and Medical Research