Figure 3. Transcriptional Changes Induced by KrasG12D Inactivation.
(A) Orthotopic xenograft tumors were generated from five independent primary iKras p53L/+ PDAC cell lines. Animals were kept on doxy for 2 weeks until tumors were fully established. Half of the animals were pulled off doxy for 24 hr at which point tumor lysate was prepared. Ras activity was measured with Raf-RBD pull-down assay.
(B) Heat maps of the genes enriched in indicated metabolism pathways illustrate the changes in gene expression upon doxy withdrawal. Expression levels shown are representative of log2 values of each replicate from either xenograft tumors or cultured parental cell lines. Red signal denotes higher expression relative to the mean expression level within the group and green signal denotes lower expression relative to the mean expression level within the group.
(C) GSEA plot of steroid biosynthesis (top), pyrimidine metabolism (middle), and O-glycan biosynthesis (bottom) pathways based on the off-doxy versus on-doxy gene expression profiles. NES denotes normalized enrichment score.
See also Figure S3.