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. 2023 Jun 23;83(17):2938–2951. doi: 10.1158/0008-5472.CAN-22-2613

Figure 1.

Figure 1. RB1 loss is not sufficient to mediate resistance to SPA. A, Growth responses of prostate cancer PDX to a 28-day course of supraphysiological testosterone. PDX lines were categorized by intact, monoallelic, or biallelic loss of RB1. Changes in tumor volume during the last 2 weeks of the study were compared by one-sided t tests with Benjamini–Hochberg-adjusted P values. B, Five-day growth assay comparing 10 nmol/L R1881 to EtOH vehicle control in LNCaP cells. C, Five-day growth assay comparing 10 nmol/L R1881 to vehicle control for LNCaP, LNCaP-RB1 knockout, and LNCaP RB1/TP53 double knockout (LNCaPDKO). D, The expression of cell-cycle progression (CCP) genes measured by RNA-seq in prostate cancer cells treated for 48 hours with vehicle control or 10 nmol/L R1881 (SPA). Data are shown as heatmaps of RNA-seq mean-centered log2 (FPKM) gene expression values. E, The expression of canonical AR-regulated genes measured by RNA-seq in prostate cancer cells treated for 48 hours with vehicle control or 10 nmol/L R1881 (SPA). F, Molecular signature (GSVA) scores determined by RNA-seq data. G, Plot of GSEA normalized enrichment scores (NES) of MSigDB Hallmark gene sets comparing 10 nmol/L R1881 (SPA)-induced gene expression changes in LNCaP and DKO cells. *, P < 0.05, by one-way ANOVA with Dunnett multiple-comparison test. Data represent the mean ± SD.

RB1 loss is not sufficient to mediate resistance to SPA. A, Growth responses of prostate cancer PDX to a 28-day course of supraphysiological testosterone. PDX lines were categorized by intact, monoallelic, or biallelic loss of RB1. Changes in tumor volume during the last 2 weeks of the study were compared by one-sided t tests with Benjamini–Hochberg-adjusted P values. B, Five-day growth assay comparing 10 nmol/L R1881 to EtOH vehicle control in LNCaP cells. C, Five-day growth assay comparing 10 nmol/L R1881 to vehicle control for LNCaP, LNCaP-RB1 knockout, and LNCaP RB1/TP53 double knockout (LNCaPDKO). D, The expression of cell-cycle progression (CCP) genes measured by RNA-seq in prostate cancer cells treated for 48 hours with vehicle control or 10 nmol/L R1881 (SPA). Data are shown as heatmaps of RNA-seq mean-centered log2 (FPKM) gene expression values. E, The expression of canonical AR-regulated genes measured by RNA-seq in prostate cancer cells treated for 48 hours with vehicle control or 10 nmol/L R1881 (SPA). F, Molecular signature (GSVA) scores determined by RNA-seq data. G, Plot of GSEA normalized enrichment scores (NES) of MSigDB Hallmark gene sets comparing 10 nmol/L R1881 (SPA)-induced gene expression changes in LNCaP and DKO cells. *, P < 0.05, by one-way ANOVA with Dunnett multiple-comparison test. Data represent the mean ± SD.