Here, we applied functional genomics approach to study step-by-step development of hepatocellular carcinoma (HCC) in the c-Myc/Tgfα transgenic mouse model of aggressive human liver cancer.
Here, we analyzed in preneoplastic and neoplastic livers from Fisher 344 and Brown Norway rats, possessing different genetic predisposition to HCC, in transforming growth factor-alpha (TGF-alpha) and c-Myc-TGF-alpha transgenic mice, characterized by different susceptibility to HCC, and in human HCC: (i) iNOS function and interactions with nuclear factor-kB (NF-kB) and Ha-RAS/extracellular signal-regulated kinase (ERK) during hepatocarcinogenesis; (ii) influence of genetic predisposition to liver cancer on these pathways and role of these cascades in determining a susceptible or resistant phenotype and (iii) iNOS prognostic value in human HCC.
Thus, TGF-beta signaling inactivation appears to cooperate with TGF-alpha in vivo to promote the formation of liver cancer that recapitulates molecular features of human HCC.
One candidate is the hepatocyte mitogen transforming growth factor alpha (TGF-alpha); in HBV-infected patients with liver cancer, TGF-alpha and HBsAg accumulate in the same hepatocytes.