THE EXPRESSION OF THE MDM2 GENE MAY BE RELATED TO THE ABERRATION OF THE P53 GENE IN HUMAN HEPATOCELLULAR-CARCINOMA

The relationship between mdm2 gene expression and p53 gene mutation in hepatocellular carcinoma (HCC) and their correlation with the invasiv eness of the disease were investigated in this study. Either the expre ssion level of the mdm2 gene or the mutation rate of the p53 gene was higher in HCC than in paratumor liver tissues. Studies on the relation ship between mdm2 and p53 revealed that mdm2 gene expression in HCC wi thout p53 mutation was higher than when there was p53 mutation, while the p53 mutation rate in HCC with mdm2 overexpression was significantl y lower than in HCC without mdm2 overexpression. Among 23 HCC with inv asion, mdm2 gene overexpression was found in 6 patients while p53 muta tion was found in the other 11 patients, and only 1 patient was found to have both mdm2 overexpression and p53 mutation. These results indic ated that either mdm2 overexpression or p53 mutation may be related to the invasiveness of HCC. Considering that an autoregulatory feedback loop between the mdm2 and p53 genes may exist, wild-type P53 can induc e the expression of mdm2 via a p53-binding site in the mdm2 gene, whil e MDM2 protein functions as a negative regulator of P53 protein. These results also suggest that mdm2 may be related to the high invasivenes s of HCC through inactivating the tumor-suppressor function of the p53 gene.