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. 2022 Jun 22;82(16):2848–2859. doi: 10.1158/0008-5472.CAN-21-3552

Figure 4.

Figure 4. AR binding associates with FASN and other lipid metabolism genes, which are regulated by AR in vitro. A, Gene-level RP score in the 16,678 AA-ARBS identifies FASN as the gene with the greatest difference in AR binding intensity in AA versus EA prostate cancer (23). B, AR binding intensity is greater in AA than EA prostate tumors at the FASN promoter, as well as several other genes that encode key lipid metabolism enzymes. Each track depicts ChIP-seq AR binding intensity in each sample. C, Normalized FASN mRNA expression in paired normal prostate tissue and prostate cancer from 24 AA and 24 EA men. Error bars reflect the standard error. D, RNA expression for FASN and KLK3 in LNCaP cells and PCA2b cells treated with vehicle, R1881 for 72 hours, or R1881 72 hours and enzalutamide for 48 hours. Expression values for cells treated with R1881 or R1881 plus enzalutamide are relative to vehicle-treated cells (black). Error bars reflect the standard error. E, FAS protein expression in 492 prostate tissue specimens from AA (102 tumor and 112 normal) and EA men (150 tumor and 128 normal) demonstrating significantly higher FAS expression in AA than EA prostate tumors. Error bars reflect the standard error. F, Metabolomic analysis of 94 lipids in 14 AA and 110 EA prostate tumors identified lipids and fatty acids present at significantly higher levels in AA prostate tumors. Box plots are displayed with a median center line, box range from the 25th to 75th percentile and whiskers extending to the most extreme observation within 1.5 times the interquartile range. NS, not significant; Padj, Padjusted.

AR binding associates with FASN and other lipid metabolism genes, which are regulated by AR in vitro. A, Gene-level RP score in the 16,678 AA-ARBS identifies FASN as the gene with the greatest difference in AR binding intensity in AA versus EA prostate cancer (23). B, AR binding intensity is greater in AA than EA prostate tumors at the FASN promoter, as well as several other genes that encode key lipid metabolism enzymes. Each track depicts ChIP-seq AR binding intensity in each sample. C, Normalized FASN mRNA expression in paired normal prostate tissue and prostate cancer from 24 AA and 24 EA men. Error bars, SE. D, RNA expression for FASN and KLK3 in LNCaP cells and PCA2b cells treated with vehicle, R1881 for 72 hours, or R1881 72 hours and enzalutamide for 48 hours. Expression values for cells treated with R1881 or R1881 plus enzalutamide were relative to vehicle-treated cells (black). Error bars, SE. E, FAS protein expression in 492 prostate tissue specimens from AA (102 tumor and 112 normal) and EA men (150 tumor and 128 normal) demonstrating significantly higher FAS expression in AA than EA prostate tumors. Error bars, SE. F, Metabolomic analysis of 94 lipids in 14 AA and 110 EA prostate tumors identified lipids and fatty acids present at significantly higher levels in AA prostate tumors. Box plots are displayed with a median center line, box range from the 25th to 75th percentile and whiskers extending to the most extreme observation within 1.5 times the interquartile range. NS, not significant; Padj, Padjusted.