Two-dimensional electrophoretic analysis of nuclear proteins from human tumors

During the last decade several strategies have been developed to identify proteins which could serve as markers in tumor biology. One avenue of great promise to detect such proteins seems to be the separation of prefractionated organelles from tumor cells by high resolution two-dimensional electrophoresis. Using detergent-lysed nuclei from several human tumor cell lines, especially from brain tumors, and two-dimensional electrophoresis, we analyzed the nuclear protein pattern obtained after sequential salt extraction of tumor cell nuclei. In addition to proteins occurring in all tumor cell lines, the pattern of different tumor cell lines exhibits considerable differences when proteins were visualized by silver staining, thus emphasizing the specificity of nuclear proteins with respect to the cell type. Even quantitative variations of the nuclear phosphoproteins 23/4 were detectable, indicating a potential correlation between their synthesis/phosphorylation and the proliferation behavior of tumor cells. The data indicate that nuclear proteins with their distinct heterogeneity and tissue specificity may represent a powerful source in determining tumor-specific proteins. The extent of chromosomal protein heterogeneity may be additionally increased by their covalent modification by nuclear kinases; therefore, tumor-specific nuclear proteins may occur as quantitative and qualitative variations.