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Updated: May 7, 2026

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

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The E2F1/DNMT1 axis is associated with the development of AR negative castration resistant prostate cancer

Conrad David Valdez1, Lakshmi Kunju, Stephanie Daignault

  • 1Department of Urology, University of Michigan, Ann Arbor, Michigan; Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan.

The Prostate
|September 17, 2013
PubMed
Abstract

Insights

Castration resistant prostate cancer (CRPC) involves loss of androgen receptor (AR) expression. The E2F1/DNMT1 axis inhibits AR transcription, contributing to CRPC development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Castration resistant prostate cancer (CRPC) research often overlooks AR gene silencing.
  • The role of AR-negative cells in CRPC progression remains understudied.

Purpose of the Study:

  • To investigate the role of AR gene expression loss in CRPC.
  • To explore the contribution of AR-negative cells to CRPC.

Main Methods:

  • Human and murine prostate cancer tissues were analyzed using immunohistochemistry for E2F1, DNMT1, and AR.
  • Murine models were treated with castration and 5'-Aza-2'-deoxycytidine (5Aza).

Main Results:

  • Increased nuclear DNMT1 and E2F1 staining observed in localized and metastatic prostate cancer (PCa) compared to normal tissue.
  • AR-positive cells decreased significantly in tumors (18%) compared to benign tissue (97%).
  • 5Aza treatment reduced DNMT1 and increased AR expression in murine models.

Conclusions:

  • The E2F1/DNMT1 pathway is activated during CRPC emergence.
  • This axis contributes to the silencing of AR transcription in CRPC.
Keywords:
DNMT1E2F1androgen receptorimmunohistochemistrymethylationtissue microarray

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