Factors that Effect Signal Transduction by the Estrogen Receptor.
Annual rept. 1 Oct 95-30 Sep 96,
NEW YORK UNIV MEDICAL CENTER NY
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This project examines the mechanism of signal transduction by the estrogen receptor ER, a hormone dependent transcriptional regulator involved in many human breast tumors. Our goal is to elucidate these mechanisms through the identification and characterization of proteins involved in the ER signal transduction pathway using genetic strategies. Our aims are to identify proteins that functionally interact with the estrogen receptor via dosage suppression screens in yeast and to isolate proteins that physically interact with the estrogen receptor using the yeast two hybrid system. Using dosage suppression analysis, we have isolated several candidate genes that when overexpressed restore the hormone-dependent activity to receptors defective in either ligand binding or receptor phosphorylation. We have also identified three proteins that physically interact with the amino-terminal transcriptional activation domain of ER using the yeast two-hybrid system. Future studies will include characterization of the gene products and analysis of their participation in transcription and receptor signaling. Since nearly half of all human breast cancers depend upon estrogen for growth, understanding how these factors function in steroid signaling may provide valuable targets for inhibiting ER action and stopping cancer growth.
- Anatomy and Physiology