Fig. 1.

A hyper-activated cholesterol-biosynthesis program is linked to RORγ in TNBC. a Heat map of activity scores of gene expression of indicated pathways with data normalized from −2 (Green) to 2 (Red) in tumors of TNBC (313 patients) and ER+ cancer (1459 patients). The gene expression datasets were from METABRIC consortium. For each of the ten metabolic pathways and cell cycle/proliferation pathway, a gene set was manually compiled, and an “activity score” was represented by the first principal component of the gene set for each of the ER+ or TNBC samples. b Relative cholesterol contents of 33 TNBC tumors and 218 ER+ tumors were measured with GC–TOFMS. Student’s t test. P = 0.0028. c Heat map display of fold changes (in log2) in cholesterol homeostasis gene expression in MDA-MB468 and MCF-7 cells treated for 48 h by agonists (blue) or antagonists (red) of indicated NRs. The concentration was 2.5 µM for each compound. The expression of indicated genes was analyzed by qRT-PCR. The experiments were repeated three times. d Scatter plots showing correlation of transcript expression between RORC and cholesterol-biosynthesis pathway in TNBC and in ER+ tumors. The Pearson correlation metric was computed by using the ‘cor’ function in R. The METABRIC dataset was used