Identification of tumor-associated protein variants during rat hepatocarcinogenesis. Aldose reductase.

Tumor-associated protein variants were detected by two-dimensional gel electrophoresis (2-DE) in soluble proteins from chemically induced rat hepatomas and transformed rat liver cell lines. Among them, a series of 8 protein variants was found localized at similar sites in 2-DE gels (33-35 kDa, with different pI values). We characterized four of them. In situ peptide mapping with limited proteolysis disclosed a significant relationship between these four individual protein spots. Their different position in 2-DE gels might be due to posttranslational modifications: one of the variants was phosphorylated, three others were modified by glycosylation. The most prominent tumor-associated protein variant of this series (spot 17) was further studied by amino acid analysis and internal amino acid microsequencing. It became evident that this variant is identical to aldose reductase (EC 1.1.1.21). This enzyme of the sorbitol pathway is expressed in the liver during embryogenesis, but is absent in adult rat liver. Our results suggest that it is reexpressed and functionally active during liver carcinogenesis.