Effects of Ca++ mobilization on expression of androgen-regulated genes: interference with androgen receptor-mediated

P E Murtha1, W Zhu, J Zhang

  • 1Department of Urology, Mayo Clinic/Foundation, Rochester, MN 55909, USA.

The Prostate
|December 16, 1997
PubMed
Abstract

Insights

Calcium signaling, through AP-1 proteins, inhibits prostate-specific antigen (PSA) gene expression by interfering with androgen receptor activity in prostate cancer cells.

Area of Science:

  • Molecular biology
  • Cancer research
  • Cell signaling

Background:

  • Prostate homeostasis relies on balanced cell growth and death.
  • Androgen deprivation increases intracellular calcium (Ca++) and AP-1 gene expression.

Purpose of the Study:

  • Investigate the impact of Ca++ on gene expression in human prostate cancer cells.
  • Elucidate the mechanism by which Ca++ affects androgen-regulated genes.

Main Methods:

  • Northern blot analysis
  • Band-shift assays
  • Transient cotransfection assays
  • Utilized Ca++ mobilizer A23187

Main Results:

  • A23187 repressed androgen-induced mRNAs for prostate-specific antigen (PSA) and hKLK2.
  • A23187 rapidly induced c-fos and c-jun mRNA levels.
  • AP-1 protein-DNA binding increased post-treatment.
  • AP-1 proteins interfered with androgen receptor (AR)-mediated gene induction.

Conclusions:

  • Ca++ mobilizers repress AR-mediated induction of PSA and hKLK2 genes.
  • AP-1 proteins are responsible for interfering with AR transactivation activity.

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