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Updated: Jun 21, 2026

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
12:13

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

Published on: November 19, 2019

Reactivation of androgen receptor-regulated TMPRSS2:ERG gene expression in castration-resistant prostate cancer

Changmeng Cai1, Hongyun Wang, Youyuan Xu

  • 1Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

Cancer Research
|July 9, 2009
PubMed

Insights

Androgen receptor (AR) reactivates TMPRSS2:ERG expression in castration-resistant prostate cancer (CRPC). This fusion gene, crucial for PC development, is restored during CRPC, potentially driving tumor progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Androgen receptor (AR)-regulated TMPRSS2:ERG fusion gene expression is implicated in prostate cancer (PC) development.
  • The regulation of TMPRSS2:ERG during androgen deprivation therapy (ADT) and its reactivation in castration-resistant PC (CRPC) remain unclear.

Purpose of the Study:

  • To determine if TMPRSS2:ERG expression is downregulated by ADT.
  • To investigate whether AR reactivates TMPRSS2:ERG expression in CRPC.

Main Methods:

  • Analysis of ERG message levels in CRPC and primary PC samples.
  • Examination of VCaP cells and xenografts to assess ERG expression changes in response to androgen withdrawal and castration.
  • Evaluation of AR and androgen synthetic enzyme mRNA levels in relapsed xenografts.

Main Results:

  • ERG message levels in fusion-positive CRPC are comparable to primary PC, suggesting TMPRSS2:ERG reactivation by AR.
  • ERG expression rapidly declined in VCaP cells and xenografts upon androgen removal/castration.
  • ERG expression was restored in relapsed xenografts, coinciding with AR reactivation and increased AR and androgen synthetic enzyme mRNA.

Conclusions:

  • TMPRSS2:ERG expression is downregulated by ADT but reactivated by AR in CRPC.
  • Reactivated TMPRSS2:ERG may contribute to tumor progression in CRPC.

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