Androgen receptor‐mediated transcriptional repression targets cell plasticity in prostate cancer

Abstract: Androgen receptor (AR) signaling remains the key therapeutic target in the management of hormone-naïve-advanced prostate cancer (PCa) and castration-resistant PCa (CRPC). Recently, landmark molecular features have been reported for CRPC, including the expression of constitutively active AR variants that lack the ligand-binding domain. Besides their role in CRPC, AR variants lead to the expression of genes involved in tumor progression. However, little is known about the specificity of their mode of action compared with that of wild-type AR (AR-WT). We performed AR transcriptome analyses in an androgen-dependent PCa cell line as well as cross-analyses with publicly available RNA-seq datasets and established that transcriptional repression capacity that was marked for AR-WT was pathologically lost by AR variants. Functional enrichment analyses allowed us to associate AR-WT repressive function to a panel of genes involved in cell adhesion and epithelial-to-mesenchymal transition. So, we postulate that a less documented AR-WT normal function in prostate epithelial cells could be the repression of a panel of genes linked to cell plasticity and that this repressive function could be pathologically abrogated by AR variants in PCa

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
ISSN: 1878-0261

Klassifikation
Medizin, Gesundheit

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2024
Urheber
Erdmann, Éva
Ould Madi Berthélémy, Pauline
Cottard, Félicie
Angel, Charlotte Zoe
Schreyer, Edwige
Ye, Tao
Morlet, Bastien
Negroni, Luc
Kieffer, Bruno
Céraline, Jocelyn

DOI
10.1002/1878-0261.13164
URN
urn:nbn:de:bsz:25-freidok-2449025
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
25.03.2025, 13:43 MEZ

Datenpartner

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Beteiligte

  • Erdmann, Éva
  • Ould Madi Berthélémy, Pauline
  • Cottard, Félicie
  • Angel, Charlotte Zoe
  • Schreyer, Edwige
  • Ye, Tao
  • Morlet, Bastien
  • Negroni, Luc
  • Kieffer, Bruno
  • Céraline, Jocelyn
  • Universität

Entstanden

  • 2024

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