Research objectives and content
Hepatocellular carcinoma (HCC) is the major type of liver tumor and is one of the most fatal cancer forms. Hepatitis B virus infection, cirrhosis, and contamination of food and water by Aflatoxin B 1, have been suggested as the most important etiologic factors for HCC. Enhanced incidence of HCC has been observed in South-European countries, including Sardegna, probably as a consequence of an increased incidence of Hepatitis B and C infection. Mutations or other structural abnormalities of p53 tumor suppressor gene are the most frequent genomic changes in human liver cancer. Indeed, p53 mutations have been detected in hepatitis B virus-positive and Aflatoxin B l-related human hepatocellular carcinomas. The purpose of the present project is to study whether functional inactivation of p53 and related genes may be responsible for the growth of HCCs using an experimental system, such as in vivo rat liver bioassays, where it is possible to analyze the multiple steps of the carcinogenic process.
This approach will support epidemiological investigations carried out in Sardegna to evaluate the role of hepatic markers in the etiology of liver cancer in terms of the Sardinian population.
Training content (objective, benefit and expected impact)
In order to dissect the role of p53 and related genes in
hepatocarcinogenesis it is necessary to use molecular biology techniques such as Western Blotting, immunoprecipitation, gel-shifts and nuclear run-off assays. However, Professor Columbano's department at the University of Cagliari does not have such expertise. Therefore I will establish these techniques and train the people in his laboratory. This should then enable them to determine the role of growth and tumor suppressor genes in liver cancer providing new molecular biological markers in their studies on the Sardinian population. These biomarkers could be useful for early detection of liver cancer.