Peptide antagonists of the human estrogen receptor

Estrogen receptor a transcriptional activity is regulated by distinct conformational states that are the result of ligand binding. Phage display was used to identify peptides that interact specifically with either estradiol- or tamoxifen-activated estrogen receptor alpha. When these peptides were coexpressed with estrogen receptor alpha in cells, they functioned as ligand-specific antagonists, indicating that estradiol-agonist and tamoxifen-partial agonist activities do not occur by the same mechanism. The ability to regulate estrogen receptor a transcriptional activity by targeting sites outside of the ligand-binding pocket has implications for the development of estrogen receptor a antagonists for the treatment of tamoxifen-refractory breast cancers.