Global gene expression profiling of spontaneous HCC in the B6C3F1 mouse identifies similarly dysregulated gene networks in mouse and humans

Hepatocellular carcinoma (HCC) is an important cause of mortality worldwide. While risk factors for HCC are well known, molecular characterization of the disease is complex, and treatment options are poor. Rodent models have been extensively used in toxicology and carcinogenicity studies for hazard identification, and the B6C3F1 mouse has been used to evaluate the effects of environmental, occupational, and other compounds in the National Toxicology Program (NTP). The high rate of spontaneous HCC in this strain has challenged its relevance to human disease. However, strategic global gene expression profiling shows dysregulation of several pathways in mouse HCC that are also important in the human disease, including re‐expression of fetal oncogenes, upregulation of protooncogenes, downregulation of tumor suppressor genes, and abnormal expression of cell cycle mediators, growth factors, apoptosis regulators, and angiogenesis and extracellular matrix remodeling factors. Although important differences in etiology and pathogenesis remain, there are fundamental similarities in global gene expression between mouse and human HCC. These data provide further relevance for the use of this model in hazard identification of compounds with potential human carcinogenicity risk, and may help us better understand mechanisms of tumorigenesis due to chemical exposure in the NTP 2‐year carcinogenicity bioassay. Research support provided by the National Toxicology Program.