Extended Data Fig. 3: Extended data in relation to Fig. 1f–j.
From: AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution
a, EZH2 mRNA expression levels in sensitive and resistant TNBC cell lines from CCLE RNAseq dataset. Sensitive cells are ranked in order of sensitivity measured by amount of cell death observed in Fig. 1c. b, Immunoblot depicting PTEN expression and PIK3CA mutational status of TNBC cell lines with Fisher’s exact test panel. Experiment was completed at least 3 times with similar results. c, Graph depicting the relative tumour volume of MDA-MB-468 orthotopic xenografts over time treated with Vehicle, AKTi (ipatasertib) and/or EZH2i (tazemetostat). Note that established tumours (100mm3) were first pretreated with vehicle or tazemetostat for 7 days prior to the addition of these agents. p value determined using mixed effects models (REML) ANOVA between AKTi and Combo. n = 10–13 tumours per arm. Data are mean ± s.e. of biological independent samples. d, Kaplan-Meier survival plot of mice bearing MDA-MB-468 orthotopic xenografts treated with vehicle or EZH2i+AKTi. Treatment ended after day 28 and animals were monitored twice weekly for humane endpoint. Significance measured by Mantel-Cox Log Rank test. e, Graph depicting percent change in body weight of tumour bearing mice treated with the indicated drugs during the treatment duration. Data are mean ± s.e. of biological independent samples. n = 6 or 7 mice per condition. g, Copy number plots of chromosomes bearing Akt3 (e), Met (f), and Ezh2 (g) isolated from untreated GEMM organoid allograft tumours from K8-CreER; Trp53fl/fl mice implanted orthotopically into nude mice. h, Photographs of H&E-stained (left) or EZH2 immunohistochemistry (right) sections of a normal mouse mammary fat pad or tumour from Fig. 1h. Scale bar = 150 μm.
