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Deviations in the pattern of soluble proteins from chemically induced primary rat hepatomas and from transformed, tumorigenic liver cell lines were determined by high resolution two-dimensional gel electrophoresis (2DE). As compared with the protein pattern of normal rat liver with approximately 1300 protein spots visible in silver-stained gels, quantitative and qualitative alterations were found in hepatomas including neoexpression of glutathione-S-transferase P, as described earlier. After correction for proliferation-related changes by comparison with gels of cells from regenerating rat liver, 30 protein variants remained, which were identically up- (n = 6) or down-regulated (n = 18) or were detected as new spots (n = 6) in primary hepatomas and transformed tumorigenic liver cell lines which are devoid of contaminating nonparenchymal cells. Seven of these variants showed a reduced expression in short-term cultured liver cells indicating dedifferentiation processes in the transformed state. Several hepatoma- and transformation-associated variants were found in clusters of similar mol. wt and/or pI, among them a complex of eight protein variants at approximately 33-35.5 kDa and a pI of approximately 6.6-7.4. Spots of this cluster show considerable changes between the investigated experimental groups and might be suited for being studied at the level of posttranslational modification during carcinogenesis.

Variant protein patterns in hepatomas and transformed liver cell lines as determined by high resolution two-dimensional gel electrophoresis (2DE)