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Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
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Comprehensive analysis of androgen receptor splice variant target gene expression in prostate cancer

Neele Wüstmann1, Julissa Reimann1, Julia Vieler1

  • 1Department of Urology, University Hospital Muenster, Germany.

Biochimica Et Biophysica Acta. Molecular Cell Research
|October 2, 2025
PubMed

Insights

This study investigated androgen receptor splice variants (AR-V) in prostate cancer, finding no distinct AR-V transcriptome driving treatment resistance. Further research is needed to understand AR-V

Area of Science:

  • Molecular Oncology
  • Prostate Cancer Research
  • Gene Expression Analysis

Background:

  • Androgen receptor (AR) signaling is crucial in prostate cancer progression.
  • AR splice variants (AR-Vs) are implicated in resistance to androgen-deprivation therapies (ARTAs).
  • The specific role of AR-Vs in treatment resistance and tumor progression remains incompletely understood.

Purpose of the Study:

  • To comprehensively analyze AR-V specific target gene expression in a model simulating co-occurrence of full-length AR (AR-FL) and AR-Vs.
  • To investigate the functional activity of clinically relevant AR-Vs (AR-V3, AR-V7, AR-V9) in prostate cancer cells.
  • To challenge the hypothesis of an AR-V specific transcriptome driving treatment resistance.

Main Methods:

  • Transfection of AR-FL and AR-V variants (AR-V3, AR-V7, AR-V9) into AR-negative PC-3 prostate cancer cells.
  • RNA sequencing to analyze differential gene expression.
  • Immunofluorescence and luciferase assays to determine protein activity.
  • Analysis of published target genes and clinical survival data.

Main Results:

  • RNA sequencing revealed minimal differences in gene expression between AR-FL and co-expressing AR-V cells.
  • AR-V7 exhibited constitutive activity, AR-V9 showed ambivalent activity, AR-V3 was inactive, and AR-FL was hormone-dependent.
  • Upregulation of EDN2 and FKBP5 was observed, but clinical analysis showed no significant impact of AR-Vs on patient survival.

Conclusions:

  • The study challenges the existence of a distinct AR-V specific transcriptome driving treatment resistance and tumor progression.
  • The molecular mechanisms by which AR-V proteins contribute to resistance to ARTA treatment require further investigation.
  • Clinical outcomes did not correlate with the presence of AR-Vs in this study cohort.
Keywords:
Androgen receptorAndrogen receptor splice variantsAndrogen receptor targeted agentsBiomarkerLiquid biopsyMetastatic castration resistant prostate cancerPredictivePrognosticTarget genes

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