The expression signature of androgen receptor splice variants and their distinctive transcriptional activities in castration-resistant prostate cancer

Stephen R. Plymate, Jun Luo

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

In a normal male genome, the androgen receptor (AR) mRNA and -protein is encoded by the single-copy androgen receptor (AR) gene located on the X chromosome. With the decoding of AR splice variants (AR-Vs) in prostate cancer, the diversity and complexity of transcribed AR sequences and the distinctive functional properties of their protein products began to be appreciated. The expression signature of AR-Vs has been characterized to some extent mainly in castration-resistant prostate cancer (CRPC), in which AR transcripts are almost always overexpressed, with or without involving genomic rearrangement of the AR gene locus. A recent tiling microarray study using CRPC specimens revealed an expression signature consisting of AR-Vs that are constitutive active, conditionally active, or inactive as transcription factors. Two constitutively active AR-Vs, AR-V7 and ARV567ES, have been characterized in more details in the context of AR-directed CRPC therapies. Suppression of canonical ligand-dependent AR-FL signaling may lead to an adaptive increase of these two AR-Vs. However, endogenously induced AR-Vs may not be sufficient to rescue the suppressed AR-FL signaling. Instead, AR-Vs may direct distinct transcriptional programs featured by genes involved in cell cycle progression. Therefore, in CRPC tumors subjected to AR-directed therapies, an adaptive shift toward AR-V-directed transcriptional programs may occur, and this shift may signify the emergence of therapeutic resistance. Future investigations focusing on clinical validation of this concept are necessary and will facilitate clinical development of novel therapies to overcome this putative resistance mechanism.

Original languageEnglish (US)
Title of host publicationAndrogen-Responsive Genes in Prostate Cancer
Subtitle of host publicationRegulation, Function and Clinical Applications
PublisherSpringer New York
Pages201-213
Number of pages13
Volume9781461461821
ISBN (Electronic)9781461461821
ISBN (Print)1461461812, 9781461461814
DOIs
StatePublished - Oct 1 2013

Keywords

  • AR-V7
  • AR-splice -variant transcriptome
  • ARV567ES
  • Androgen receptor
  • Androgen receptor splice variant
  • Castration-resistant prostate cancer
  • Cell cycle

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'The expression signature of androgen receptor splice variants and their distinctive transcriptional activities in castration-resistant prostate cancer'. Together they form a unique fingerprint.

  • Cite this

    Plymate, S. R., & Luo, J. (2013). The expression signature of androgen receptor splice variants and their distinctive transcriptional activities in castration-resistant prostate cancer. In Androgen-Responsive Genes in Prostate Cancer: Regulation, Function and Clinical Applications (Vol. 9781461461821, pp. 201-213). Springer New York. https://doi.org/10.1007/978-1-4614-6182-1_13