Extended Data Fig. 7: AR agonism sustains growth inhibition in a ZR-75-1 xenograft tumor model.
From: The androgen receptor is a tumor suppressor in estrogen receptor–positive breast cancer
a, Growth curves for ZR-75-1 xenograft tumors treated with E2 alone (n = 6) or in combination with AR agonists (DHT or Enobosarm (SARM); n = 6 and 7 tumors, respectively) or an AR antagonist (Enzalutamide; n = 6). Data represented as mean ± SEM. b, Representative IHC for ER, PR (encoded by ER target gene PGR), AR, and SEC14L2 (encoded by AR target gene SEC14L2) for ZR-75-1 xenograft tumors harvested 5 days post-treatment. Scale bars represent 100 µm. c, Quantification of Ki67-positivity from n = 4 (E2 + Veh, E2 + SARM and E2 + Enz) or n = 5 (E2 + DHT) ZR-75-1 xenograft tumors harvested 5 days post-treatment. Boxes in the graph show minimum and maximum (bottom and top lines, respectively) and mean (line within the boxes). Data was analyzed using a two-tailed, unpaired t-test (t = 17.36, 11.37, and 0.7941; df = 7, 6, and 7; for E2 + Veh vs. E2 + DHT (p < 0.0001), E2 + SARM (p < 0.0001), and E2 + Enza (p = 0.4574), respectively). Asterisks denote statistical significance; ****p < 0.0001, d, Ki67 IHC images in each treatment arm associated with (c). Scale bars represent 100 µm. Images are representative of n = 4 (E2 + Veh, E2 + SARM and E2 + Enz) or n = 5 (E2 + DHT) independent tumors. e, RNA-seq heatmap of all differentially expressed genes (FDR < 0.05) in 5 day-treated ZR-75-1 tumors demonstrates clustering of AR agonists (DHT and SARM) away from Vehicle (Veh) and the AR antagonist Enzalutamide (Enz). f, Independent RT-qPCR validation of select ER and AR target genes. Data represents an average normalized gene expression of 4 (E2 + Veh, E2 + Enz, E2 + SARM) or 5 (E2 + DHT) replicate tumors. NS, not significant.
