Expression of tumor-associated protein variants in chemically induced rat hepatomas and transformed rat liver cell lines determined by two-dimensional electrophoresis.

High resolution two-dimensional electrophoresis (2-DE), using the rat liver as a model, was applied to study hepatocarcinogenesis induced by different chemical carcinogens. Several tumor-associated protein variants were detected by 2-DE in chemically induced rat hepatomas and transformed rat liver cell lines compared to normal rat liver tissue. Proliferation-related protein changes and/or protein alterations due to culture conditions were corrected for by comparison with 2-DE patterns of isolated cells from regenerating liver and short-term cultivated liver cells. Some of the tumor-associated variants were further characterized: (i) By peptide mapping with limited proteolysis we detected clear relationships between several variants. (ii) By studying post-translational modifications phosphorylated and glycosylated variants could be determined. (iii) A tumor-associated protein variant was identified by amino acid analysis and amino acid sequencing.