We have found that, compared to primary hepatocytes, hepatoma cell lines display aberrant insulin—receptor tyrosine kinase signaling consisting in elevated basal phosphorylation of AKT specifically at Thr 308 and constitutively activated RAS-MAPK signaling, which were resistant to the effects of the dominant negative Ras mutant H-RAS17N. The gene discussed is INS; the disease is hepatocellular carcinoma.