Inhibition of mTOR attenuates the initiation and progression of BRCA1-associated mammary tumors

We conducted global proteome and phosphoproteome profiling of vehicle- and everolimus-treated tumors from 17 mice that were allografted with spontaneously developed mammary tumors from Brca1co/coMMTV-Cre mice using LC-MS/MS. The Proteome Discoverer analysis identified 9,625 proteins having two unique sibling peptides and more and 35,142 phosphopeptides with a peptide- and protein-level FDR of 1% using SEQUEST-HT algorithm. We defined everolimus-sensitive and resistant tumors based on proteome and phosphoproteome data, and identified protein and phosphopeptide signatures defining each cluster. Pathway enrichment analysis of these signatures further revealed that leukotriene-neutrophil activation pathways were upregulated in everolimus-resistant tumors.