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Definition of the Cellular Mechanisms which Distinguish Between Estrogen Receptor Agonists and Antagonists
Annual summary rept. 1 Jul 2000-30 Jun 2001
DUKE UNIV MEDICAL CENTER DURHAM NC
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Estrogen is mitogenic in most estrogen receptor ER positive breast cancers and the use of anti-estrogen like tamoxifen has been quite successful in the treatment of this disease. Although patients initially respond well to anti-estrogens, resistant tumors often develop within 5-10 years of treatment. The purpose of this research is to develop mechanistically distinct therapeutics by directly blocking the interaction of ER with coactivator proteins required for its activity. In the previous funding period, we reported the identification of conformational peptide probes that detect the estrogen receptor conformations. In this granting period, we have extended our study in the following two directions. 1 Developing high affinity ER-specific peptides for targeting ER activity. 2 Identifying novel ER-interacting cofactor proteins that may facilitate the elucidation of ER pharmacology, and to validate these receptorcofactor interaction surfaces as targets for therapeutic intervention.
APPROVED FOR PUBLIC RELEASE