Mouse models and generation of cell lines

All mice used in the study were housed and treated according to the guidelines provided by the Fred Hutch Institutional Animal Care and Use Committee. The Kras G12D LSL and Trp53 floxed alleles were maintained on a C57BL6 background. Heterozygous Kras G12D LSL/+ alone (termed Kras) or in combination with Trp53 fl/fl homozygous alleles (termed KP) were used for experiments. Mice 2 months or older were utilized for intratracheal instillation of lentiviral particles in a BSL2 facility (DuPage et al., 2009). For generation of KP mouse lines, tumors were collected using sterile surgical instruments from endpoint KP mice. Tumors were mechanically disaggregated using a wide bore pipette tip and cultured in DMEM supplemented with 10% FBS and antibiotics. Cells were passaged until tumor cells outgrew stromal contaminants (immune cells, fibroblasts, and endothelial cells) and used for subsequent downstream applications.