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. Author manuscript; available in PMC: 2018 Feb 1.
Published in final edited form as: J Steroid Biochem Mol Biol. 2016 Apr 28;166:28–37. doi: 10.1016/j.jsbmb.2016.04.016

Fig. 1. Canonical/resistance AR signaling and AR-V structure.

Fig. 1

A. Hypothetical timeline representing progression of primary prostate cancer to castration resistant prostate cancer. B. Tissues and other clinical material (CTCs-circulating tumor cells; ctDNA-cell free, circulating tumor DNA) available for interrogation of alterations in the androgen/AR pathway. C. Illustration of normal and aberrant modes of androgen/AR signaling. The upper left quadrant summarizes canonical AR signaling that occurs in normal development and prostate cancer. In this setting, DHT binds AR, which promotes AR translocation to the nucleus and transcriptional activation. Components of this axis targeted by abiraterone and enzalutamide are indicated. The top right quadrant illustrates how amplification of the AR locus results in AR protein overexpression, which is highly sensitive to castrate levels of androgen. The bottom right quadrant illustrates the domain structure of AR-Vs. The expanded view displays exon composition of 5 separate mRNAs that encode discrete AR-Vs that are detailed within the text. The bottom left quadrant shows how mutations in the AR ligand binding domain can convert non AR ligands and AR antagonists to agonists, leading to transcription of AR target genes.