Temporal and Spatial Dynamics of Androgen Receptor Conformation and Interactions in Prostate Cancer Cells

Abstract

Our long-term goal is to correlate the undesired escape from androgen deprivation therapy with specific molecular events in Androgen Receptor signaling in order to determine the best molecular targets for prostate cancer treatment. Studies supported by this grant indicate that the failure of tumors to respond to anti-androgen therapy corresponded best with an increased nuclear transport of AR. However, an intramolecular fold and AR dimerization, both activated abnormally by heterologous hormones (estrogen and progestin) and measured by fluorescence resonance energy transfer of CFP and YFP-tagged ARs), also was linked to four different AR mutants associated with treatment-refractory prostate proliferation. High throughput methods were developed to measure AR folding, dimerization and nuclear transport. These methods will facilitate the future identification of new drugs that block AR folding, dimerization and nuclear transport and that may prove useful in treatment-refractory therapy.

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Document Details

Document Type
Technical Report
Publication Date
Nov 01, 2007
Accession Number
ADA477478

Entities

People

  • Fred Schaufele

Organizations

  • University of California, San Francisco

Tags

DTIC Thesaurus Topics

  • Acquisition
  • Androgen Receptors
  • Androgens
  • Birds
  • Cell Line
  • Cell Nucleus
  • Cells
  • Chemistry
  • Diseases And Disorders
  • Energy Transfer
  • Fluorescence
  • Hormones
  • Molecules
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Proteins

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular Genetics
  • Prostate Cancer Biology.