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The androgen receptor pathway is by-passed in prostate cancer cells generated after prolonged treatment with

Alfred Hobisch1, Andreas Fritzer, Barbara Comuzzi

  • 1Department of Urology, General Hospital Feldkirch, Feldkirch, Austria.

The Prostate
|November 23, 2005
PubMed
Abstract

Insights

Prostate cancer cells treated with anti-androgen bicalutamide did not show enhanced androgen receptor signaling. This suggests a need for differentiated strategies to target androgen receptors in therapy-resistant prostate cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Androgen receptor (AR) signaling is crucial in prostate cancer progression.
  • Therapy resistance to anti-androgens is a significant clinical challenge.
  • The AR pathway's role in resistance to chronic non-steroidal anti-androgen treatment requires further investigation.

Purpose of the Study:

  • To investigate the androgen receptor signaling pathway in prostate cancer cells resistant to anti-androgen therapy.
  • To characterize a novel cell line, LNCaP-Bic, developed through prolonged exposure to androgen and bicalutamide.
  • To assess the impact of androgen, bicalutamide, and tocopherol succinate on cell proliferation and AR activity.

Main Methods:

  • Generation of a novel LNCaP-Bic cell subline resistant to bicalutamide.
  • Cell proliferation assays in the presence/absence of androgen, tocopherol succinate, and bicalutamide.
  • Western blot analysis for androgen receptor expression.
  • Luciferase reporter assays to measure androgen-responsive gene activity.

Main Results:

  • LNCaP-Bic cells exhibited a threefold increase in proliferation compared to control LNCaP cells.
  • Neither R1881 (synthetic androgen) nor bicalutamide affected LNCaP-Bic cell growth.
  • Androgen receptor expression levels were similar between LNCaP-Bic and parental LNCaP cells.
  • R1881-induced reporter gene activity was reduced by 56% in LNCaP-Bic cells.
  • Tocopherol succinate inhibited proliferation only in parental cells but downregulated AR and PSA in both cell lines.

Conclusions:

  • Androgen receptor-mediated signaling is not upregulated in prostate cancer cells selected with bicalutamide.
  • These findings suggest that alternative or differentiated approaches are necessary for targeting AR in castration-resistant prostate cancer.
  • The study highlights the complex mechanisms underlying resistance to endocrine therapy in prostate cancer.

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