Models d'hepatocarcinogènesi: animals transgènics que expressen oncògens i antioncògens

The incidence of liver carcinoma is increasing, since it is associated to cirrhotic process mainly related to alcohol ingestion or viral hepatitis B or C. The goals of this project are, on the one hand, the study of the mechanisms leading to the onset of neoplasia, and, on the other, to create specific animal models of hepatocelular carcinomas to be used in developing new therapies. For this reason, transgenic animals carrying chimeric genes containing the P-enopyruvate carboxykinase promoter/regulatory region linked to mutated Ha-ras, c-myc and mutated p53 oncogenes, and to p53 and Krev-1 tumor supressor genes will be created. This promoter is tissue- and development-specific, and it is very well regulated by different hormones (insulin, glucagon, glucocorticoids, etc), in such a manner that even dietary changes can abolish or activate its expression. Once first animals will be obtained