Concurrent Disruption of Ras-Erk and NF-κB Pathways Induces Circadian Deregulation and Hepatocarcinogenesis

Mice with hepatocyte-specific deletion of both Shp2 and IkkB were generated, which disrupted basal levels of Ras-ERK and NF-kB signaling. These mice exhibited accelerated liver tumor formation compared to either single knockout alone. RNA-Seq analysis of whole liver and isolated hepatocytes from all genotypes were performed to identify tumor-promoting factors in the DKO model. Along with inflammatory and 24 samples were analyzed from whole liver samples or isolated hepatocytes from 2-month old male mice with knockout of Shp2 and/or IkkB; 3 biological replicates per genotype; WT C57/BL6 mice used as controls