Isoform specific activities of androgen receptor and its splice variants in prostate cancer cells

Androgen receptor (AR) signaling continues to drive castration resistant prostate cancer (CRPC) in spite of androgen deprivation therapy (ADT). Constitutively active shorter variants of AR, lacking the ligand binding domain, are frequently expressed in CRPC and have emerged as a potential mechanism for prostate cancer to escape ADT.  ARv7 and ARv567es are two of the most commonly detected variants of AR in clinical samples of advanced, metastatic prostate cancer. It is not clear if variants of AR merely act as weaker substitutes for AR or can mediate unique isoform specific activities different from AR. In this study, we employed LNCaP prostate cancer cell lines with inducible expression of ARv7 or ARv567es to delineate similarities and differences in transcriptomics, metabolomics and lipidomics resulting from the activation of AR, ARv7 or ARv567es. While the majority of target genes were similarly regulated by the action of all three isoforms, we found a clear difference in transcripto...