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Androgen-mediated resistance to apoptosis

Ronan N T Coffey1, R William G Watson, Amanda J O'Neill

  • 1Department of Surgery, Mater Misericordiae Hospital, University College Dublin, Dublin, Ireland. research@profsurg.iol.ie

The Prostate
|November 14, 2002
PubMed
Abstract

Insights

Androgen (5-alphaDHT) protects prostate cancer cells from apoptosis by reducing pro-apoptotic gene expression. This survival effect is mediated by NF-kappaB, suggesting a general survival signaling role for androgens.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Endocrinology

Background:

  • Androgens exhibit a protective effect in prostate cancer cells (LNCaP).
  • Mechanisms, especially androgen's impact on apoptosis-related gene expression, remain underexplored.

Purpose of the Study:

  • Investigate androgen's influence on apoptotic sensitivity.
  • Analyze androgen's effect on caspases and Bcl-2 family gene expression.
  • Determine androgen's role in NF-kappaB activation.

Main Methods:

  • Utilized LNCaP cell line for experiments.
  • Assessed apoptosis following radiation and etoposide treatment.
  • Examined gene expression of caspases and Bcl-2 family members.
  • Employed gel mobility shift assay to study NF-kappaB activation.

Main Results:

  • 5-alpha-Dihydrotestosterone (5-alphaDHT) conferred resistance to apoptosis induced by radiation and etoposide.
  • This protection correlated with decreased expression of caspases and pro-apoptotic Bcl-2 family genes.
  • 5-alphaDHT failed to protect NF-kappaB-inhibited LNCaP cells and androgen-insensitive cell lines (PC-3, DU-145).

Conclusions:

  • 5-alphaDHT increases the apoptotic threshold in LNCaP cells by modulating pro-apoptotic gene expression.
  • Androgen may act as a survival signal against various apoptotic pathways.
  • NF-kappaB is hypothesized to be a key mediator in androgen-mediated survival signaling.

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