Portal de Periódicos da CAPES

Peptide Antagonists of the Human Estrogen Receptor

1999; American Association for the Advancement of Science; Volume: 285; Issue: 5428 Linguagem: Inglês

10.1126/science.285.5428.744

1095-9203

John D. Norris, Lisa A. Paige, Dale J. Christensen, Ching‐yi Chang, Maria R. Huacani, Daju Fan, Paul T. Hamilton, Dana M. Fowlkes, Donald P. McDonnell,

Growth Hormone and Insulin-like Growth Factors

Estrogen receptor alpha 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 alpha transcriptional activity by targeting sites outside of the ligand-binding pocket has implications for the development of estrogen receptor alpha antagonists for the treatment of tamoxifen-refractory breast cancers.