Figure 1.

Establishment of enzalutamide (ENZ)-resistant prostate cancer (PCa) cellular models. (A) Experimental approach to establish PCa resistance in a mouse model and to derive castration-resistant but ENZ-sensitive, and ENZ-resistant cell lines. Cx: surgical castration, Tx: ENZ treatment. (B) Viable cell count assay on VCaP^CRPC and VCaP^ER performed with and without increasing quantities of ENZ. n = 4 biological replicates. (C) Western blots showing expression of androgen receptor (AR) and resistance-specific splice variant AR-V7 in VCaP^CRPC and VCaP^ER (left). Quantifications of Western Blot signal intensity relative to VCaP^CRPC and normalized to total protein (right). n = 3 biological replicates. (D) Schematic for analysis of transcriptome, translatome and proteome in PCa cell lines: Transcriptome and proteome from VCaP, VCaP^CRPC and VCaP^ER and translatome from VCaP^CRPC and VCaP^ER. (E) Heatmap and (F) boxplots of correlation coefficients for VCaP^CRPC and VCaP^ER proteomes with proteomes from patient samples. BPH: Benign prostate hyperplasia. T1C: tumor not detectable by palpation but detected upon needle biopsy. T2: tumor detectable by palpation but confined to the prostate. CRPC: Castration resistant prostate cancer. *P-value < 0.05; **P-value < 0.01; ***P-value < 0.001; ns indicates a non-significant P-value.