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Androgen receptor variants: RNA-based mechanisms and therapeutic targets.

Authors
  • Tietz, Kiel T1
  • Dehm, Scott M1, 2
  • 1 Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
  • 2 Departments of Laboratory Medicine and Pathology and Urology, University of Minnesota, Minneapolis, MN 55455, USA.
Type
Published Article
Journal
Human Molecular Genetics
Publisher
Oxford University Press
Publication Date
Sep 30, 2020
Volume
29
Issue
R1
Identifiers
DOI: 10.1093/hmg/ddaa089
PMID: 32412639
Source
Medline
Language
English
License
Unknown

Abstract

Prostate cancer is the second leading cause of male cancer death in the United States. The androgen receptor (AR) transcription factor is a master regulator of normal glandular homeostasis in the prostate, as well as growth and survival of prostate cancer cells. Therefore, AR-targeted therapies are effective for improving overall survival of patients with advanced prostate cancer that is incurable by surgery or radiation. However, prostate cancer will inevitably progress on AR-targeted therapies to a castration-resistant prostate cancer (CRPC) phenotype that accounts for virtually all prostate cancer-specific death. mRNA transcript variants of the AR gene are expressed in CRPC cells and can be translated to produce AR variant (AR-V) proteins that function as ligand-independent, constitutively active transcription factors. AR-Vs are able to support growth of CRPC cells by promoting expression of AR target genes that are normally suppressed by AR-targeted therapies. Knowledge of mechanisms that govern expression of AR-Vs is incomplete. Studies have shown genomic rearrangements of the AR gene underlie expression of diverse AR-Vs in certain CRPC tumors, but post-transcriptional processes represent a broader regulatory mechanism for expression of AR-Vs in CRPC. This review focuses on alternative splicing, 3' end processing, miRNA-mediated mRNA repression, of AR and AR-V expression and the potential these mechanisms hold as therapeutic targets for CRPC. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]

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