POINT MUTATION OF ORNITHINE DECARBOXYLASE GENE IN HUMAN HEPATOCELLULAR-CARCINOMA

Ornithine decarboxylase (ODC) plays an important role in cell growth, and its activity is regulated by many mechanisms. The biochemical char acteristics of ODC in malignant cells differ from those of ODC in norm al cells. To determine whether novel changes occur in ODC in neoplasti c tissue, we compared the nucleotide sequence of ODC cDNA obtained fro m human hepatoma tissue as determined by reverse transcriptase-PCR wit h that of ODC cDNA obtained from nontumorous tissue in the same patien ts, There were three point mutations accompanied by replacements of am ino acids in hepatoma tissue with other amino acids or a stop codon. I n one poorly differentiated hepatoma, codon 415, CAA was concerted to TAA, resulting in replacement of Gln-415 by a stop codon. The mutated ODC protein produced by translation in a reticulocyte-lysate protein s ynthesizing system was truncated and stabilized in an ATP antizyme-dep endent degradation system. These findings suggest that formation of a truncated and stabilized ODC protein due to point mutation is one reas on why ODC activity is high in human hepatoma tissue.