Methods for Identifying and Quantifying mRNA Expression of Androgen Receptor Splicing Variants in Prostate Cancer

Methods Mol Biol. 2016:1443:165-77. doi: 10.1007/978-1-4939-3724-0_11.

Abstract

Constitutively active androgen receptor (AR) variants (AR-Vs) lacking the AR ligand-binding domain have been identified as drivers of prostate cancer resistance to AR-targeted therapies. A definitive understanding of the role and origin of AR-Vs in the natural history of prostate cancer progression requires cataloging the entire spectrum of AR-Vs expressed in prostate cancer, as well as accurate determination of their expression levels relative to full-length AR in clinical tissues and models of progression. Exon constituency differences at the 3' terminus of mRNAs encoding AR-Vs compared with mRNAs encoding full-length AR can be exploited for discovery and quantification-based experiments. Here, we provide methodological details for 3' rapid amplification of cDNA ends (3' RACE) and absolute quantitative RT-PCR, which are cost-effective approaches for identifying new AR-Vs and quantifying their absolute expression levels in conjunction with full-length AR in RNA samples derived from various sources.

Keywords: AR splice variant; Absolute quantification; Alternative splicing; Androgen receptor; Castration-resistant; Prostate cancer; RT-PCR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alternative Splicing*
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Prostatic Neoplasms / genetics*
  • RNA, Messenger / genetics*
  • Real-Time Polymerase Chain Reaction / methods*
  • Receptors, Androgen / genetics*
  • Tumor Cells, Cultured

Substances

  • AR protein, human
  • RNA, Messenger
  • Receptors, Androgen