RNA-sequencing of whole lungs from mice with activating Kras mutations and epithelial Stat3 deletion

We have previously shown that Kras mutant-induced lung tumors in CCSPCre/LSL-K-rasG12D mice (CC-LR) exhibited Stat3 activation. Here we sought to study the role of epithelial Stat3 in Kras-mutant lung tumor oncogenesis through derivation of a lung epithelial specific CC-LR/Stat3 conditional knockout (LR/Stat3D/D or LRDD) model. Analysis of tumor burdens revealed marked gender disparity following epithelial Stat3 deletion, LRDD males exhibited increased tumor burdens compared to male CC-LR animals whereas female LRDD mice displayed attenuated tumor development when compared to female CC-LR littermates. We then performed RNA-sequencing of whole lungs from the mice in order to understand global expression programs that may underlie this gender-specific effect of epithelial Stat3 deletion. Overall design: Frozen whole lungs from 14 weeks old male and female CC-LR and LRDD mice (n= 3 in each subgroup by gender and genotype; n = 12 total) were excised and total RNA isolated. Total RNA was sequenced using the Ion Torrent Proton and analyzed for differential gene expression that are modulated by gender, genotype and both.