Fig. 6
Pathway analysis reveals key differences in Rb pathway components and upregulation of druggable targets in mammary tumors. A Clustering of normalized RNA-seq data for genes in the Rb pathway revealed low levels of Rb1 mRNA in the majority of tumors (regardless of genotype), and additional dysregulation of the pathway by increased expression of Ccne1 (Cyclin E), Cdkn2A (Cyclin-dependent kinase inhibitor 2A; p16), Rbl1 (Retinoblastoma-like 1; p107), Cdk2 (Cyclin-dependent kinase 2), Cdkn1b (Cyclin-dependent kinase inhibitor 1B, p27), Cdkn1a (Cyclin-dependent kinase inhibitor 1A; p21) and Cdk4 (Cyclin-dependent kinase 4) (highlighted in purple frame) in tumors with Rbf inhibition compared to the normal mammary glands and increased expression of Ccnd1 (Cyclin D1), Cdk4, Rbl2 (Retinoblastoma-like 2; p130) and Cdk6 (Cyclin-dependent kinase 6) (highlighted green frame) in B1/P tumors. B Expression of genes in the Rb pathway was analyzed by RT-qPCR on a set of 3 to 5 tumors from each genotype. Expression was normalized to normal mammary gland shown on the left side of each graph for illustration. Comparison of expression was performed between tumors of different genotype using One-tail ANOVA statistical analysis. C Single-sample GSEA (ssGSEA) heatmap highlights canonical pathways that were significantly enriched in mammary tumors