Molecular Determinants of Estrogen Receptor Alpha Stability

Abstract

Our studies show that the ligand binding domain (LBD) of estrogen receptor alpha (ER ) is important in mediating ICI 182,780 (ICI)-induced degradation of ER . Further, we show that a single residue within helix 12 (H12) is specifically important in allowing for the degradation of ER following treatment with ICI. That this residue is not conserved between ER and ER may explain why ER does not undergo rapid ICI-mediated degradation, and may also explain why ICI is not as effective at reducing the basal activity of ER . This study is a key first step in elucidating the mechanism by which ER undergoes ligandmediated degradation, and hopefully future studies will enable the identification of points in the degradation pathway that can be exploited pharmacologically for the treatment of breast cancer, and potentially other malignancies that are dependent upon estrogen signaling for continued growth.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2007
Accession Number
ADA473731

Entities

People

  • Carolyn D. Dusell

Organizations

  • Duke University

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cells
  • Degradation
  • Department Of Defense
  • Diseases And Disorders
  • Electronic Mail
  • Estrogens
  • Hormone Antagonists
  • Identification
  • Indicator Dyes
  • Information Operations
  • Neoplasms
  • Tissue Extracts

Readers

  • Breast cancer cell signaling and growth regulation.