The Role of Ca2+ and Calmodulin in Estrogen Receptor Function and Tamoxifen Resistance

Abstract

The purpose of this proposal is to evaluate the participation of Ca2+ and calmodulin in estrogen receptor (ER) function and tamoxifen resistance. The focus is directed towards the interaction between calmodulin and ER in ER signaling, as well as the possible involvement of Ca2+ and calmodulin in tamoxifen resistance. Major findings to date are: (i) calmodulin binds directly to ER and stabilizes the receptor; (ii) calmodulin protects ER from degradation in the proteasome pathway; (iii) calmodulin is necessary for estrogen-stimulated transcriptional activation by ER; (iv) the effect of calmodulin in ER transcriptional activation is independent of its effect on ER stability; and (v) inhibition of calmodulin function in the nucleus, but not at the plasma membrane, eliminates estrogen-induced transcriptional activation by ER. These data reveal that calmodulin is a component of both ER stability and ER transcriptional activity. This information could have potential therapeutic implications in patients with breast cancer.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2003
Accession Number
ADA416274

Entities

People

  • David B. Sacks

Organizations

  • Brigham and Women's Hospital

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Alkenes
  • Breast Cancer
  • Cell Line
  • Cell Membrane
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Confocal Microscopy
  • Epithelial Cells
  • Estrogens
  • Health Services
  • Molecular Biology
  • Neoplasms
  • Proteins
  • Resistance
  • Tumor Cell Line

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.