Figure 4

ResA and ResB cells have acquired a non-neuroendocrine AR indifferent phenotype. (a) AR protein expression measured by western blotting under normal growth conditions. The uncropped blots are shown in Supplementary Fig. 5. (b) Standardized gene expression (z-score) of the MSigDB Hallmark “Androgen Response” signature upon treatment of the cells with 10 nM DHT, 10 µM enzalutamide (enz), combination of the two or vehicle for 18 hours. The dashed line represents the median of vehicle treated LNCaP. (c) Log scaled FPKM (fragments per kilobase million) mRNA expression of the neuroendocrine markers MYCN, CHGA, GRP (bombesin), NCAM1 (CD56), SYP, and ENO2 in the cell lines in conditions similar to their respective growth medium (+10 nM DHT for all cell-lines; +10 µM enz for ResA/ResB). (d) Dose response curves showing the relative proliferation rate in androgen deprived (DCC) medium supplemented with increasing concentrations of the highly potent synthetic androgen R1881. All measurements are normalized to vehicle treated cells and set to 100. The shaded areas and error bars indicate the 95% confidence interval.