Comprehensive analysis of androgen receptor splice variant target gene expression in prostate cancer

This study aimed to comprehensively analyze AR-V specific target gene expression using a physiological system that simulates the actual situation of AR-FL and AR-V co-appearance in prostate cancer patients. Clinically described AR splice variants AR-V3, AR-V7 and AR-V9 were transfected along with AR-FL in AR-negative prostate cancer PC-3 cells. RNA sequencing analysis showed only slight differences in differentially expressed genes between AR-FL and AR-V co-expressing cells compared to solely AR-FL expressing cells. Immunofluorescence analysis and luciferase assays revealed hormonal dependency of AR-FL, constitutive activity of AR-V7, and ambivalent activity of AR-V9, while AR-V3 showed no activity. Analysis of a set of published target genes showed steady upregulation of EDN2 and FKBP5. Yet, clinical analysis revealed no significant differences in overall survival data in prostate cancer patients. The study challenges the existence of an AR-V specific transcriptome responsible for treatment resistance and tumor progression and highlights the need for further investigation into the molecular mechanism by which AR-V proteins route resistance to ARTA treatment.