TNBC cells have impaired pitavastatin-induced SREBP-2 activation. A, RNA-seq was performed in TN (MDA-MB-468) and ER-positive (T47D) breast cancer cells treated with DMSO, AZD5363 (MDA-MB-468, 10 µmol/L; T47D, 0.25 µmol/L), pitavastatin (1 µmol/L), or a combination of AZD5363 and pitavastatin for 24 or 48 hours. Data for SREBF2 target genes are represented as log2 counts per million for each replicate (N = 3 biological replicates per condition). B, TN (MDA-MB-468) and ER-positive (T47D) breast cancer cells were transfected with siControl (siCtrl), siSREBF-1, or siSREBF-2 for 24 hours and then treated with DMSO, AZD5363 (MDA-MB-468, 15 µmol/L; T47D, 0.25 µmol/L), pitavastatin (2 µmol/L), or a combination of AZD5363 and pitavastatin for 72 hours, and cell density was measured by SRB assay. Data are represented as mean ± SD (N = 3 technical replicates). Statistical analysis was performed using two-way ANOVA with Tukey multiple comparison test (*, significant differences compared with the matched treatment condition in the siCtrl cells). C, Immunoblots of NPC1, HMGCR, SREBP-1/2, unprenylated RAP1A, and β-actin in TN (SUM159, MDA-MB-468, and BT20) and ER-positive (T47D, MCF7, BT474) breast cancer cell lines treated with DMSO or 2 µmol/L pitavastatin for 2, 6, or 24 hours. **, P = 0.0021; ***, P = 0.0002; ****, P < 0.0001; ns, not significant. cpm, counts per million.