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Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
13:19

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Published on: November 2, 2013

Androgen receptor mutations identified in prostate cancer and androgen insensitivity syndrome display aberrant ART-27

Wenhui Li1, Claudio N Cavasotto, Timothy Cardozo

  • 1Department of Microbiology, New York University Cancer Institute, New York University School of Medicine, New York, New York 10016, USA.

Molecular Endocrinology (Baltimore, Md.)
|May 28, 2005
PubMed

Insights

Aberrant androgen receptor (AR) interactions with coactivators like ART-27 may drive diseases such as prostate cancer. Specific AR mutations impair ART-27 function, suggesting a role in disease pathogenesis.

Area of Science:

  • Molecular Biology
  • Genetics
  • Endocrinology

Background:

  • Androgen receptor (AR) transcriptional activity relies on coregulatory molecules.
  • Dysfunctional AR-coregulator interactions are implicated in diseases like prostate cancer and androgen insensitivity syndrome (AIS), but direct evidence is limited.
  • ART-27 is a novel AR N-terminal coactivator linked to AR-mediated growth inhibition.

Purpose of the Study:

  • To investigate how naturally occurring AR mutations found in prostate cancer and AIS affect the receptor's response to the coactivator ART-27.
  • To determine if altered AR-ART-27 interactions contribute to the pathogenesis of AR-related diseases.

Main Methods:

  • Analysis of AR mutations from prostate cancer and AIS patients.
  • Assessing the transcriptional response of mutated ARs to ART-27 and p160 coactivators.
  • Quantifying ART-27 protein association with wild-type and mutant ARs.

Main Results:

  • Most AR mutations enhanced transcriptional activity in response to ART-27.
  • AR mutations P340L (prostate cancer) and E2K (AIS) exhibited reduced transcriptional responses to ART-27, unlike their response to p160 coactivators.
  • ART-27 binding was reduced with AR E2K but surprisingly increased with AR P340L, despite decreased transcriptional activity.

Conclusions:

  • Aberrant AR-coactivator interactions, specifically with ART-27, can interfere with coactivator function and suppress AR activity.
  • These disruptions in ART-27 coactivation may play a role in the development of prostate cancer and AIS.
  • Understanding these molecular mechanisms is crucial for disease pathogenesis research.

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