Figure 6. AR-V7 retains the ability to drive transcription independently of heterodimerization with AR-FL.
A & B. Luciferase assays in PC-3 (A) or LNCaP cells (B) co-transfected with an ARE-driven luciferase reporter construct and mock control or indicated AR-V7 expression plasmid showing that, in contrast to AR-V7D, AR-V7FD, and AR-V7P, AR-V7F retains the ability to transactivate. *, P < 0.001 from mock. C & D. RNA-seq analyses of LNCaP cells stably expressing cumate-inducible AR-V7WT or AR-V7MT showing that the transcriptional program induced by AR-V7WT is in general maintained in AR-V7F-expressing cells, but not in AR-V7FD-expressing cells. C: Clustering analysis was performed using genes that were differentially expressed between AR-V7WT-expressing cells and the mock control cells. D: Relative expression levels from the RNA-seq data showing that AR-V7F retains the ability to induce the expression of KLK3, FKBP5, and TMPRSS2 but loses the ability to induce GNMT and FASN expression. *, FDR < 0.01 from mock. E. ChIP assay showing that the similarity and/or difference between the wildtype and mutant AR-V7 in regulating target genes can be largely explained by their ability/inability to bind to the 5’-regulatory region of these genes. The results were from 3 independent experiments. *, P < 0.01 from mock.