Differences in the nuclear proteins of normal and malignant liver cells.

Immunological tests and 2-dimensional gel electrophoresis revealed differences between the nuclear proteins from normal and malignant liver cells. Immunization of rabbits with a nuclear nonhistone protein fraction isolated from normal mouse liver resulted in antisera that in immunofluorescence gave nuclear staining in sections of normal liver, but did not stain nuclei of a transplantable mouse hepatoma. Antisera prepared against a nuclear protein fraction from the hepatoma allowed immunofluorescent staining of hepatoma nuclei but did not stain nuclei from normal liver. Nuclei in liver regeneration after injury caused by administration of carbon tetrachloride stained with antiserum against normal nuclei but not with antisera against hepatoma nuclei. Neither antiserum stained nuclei in fetal liver cells. The presence of differing sets of nuclear proteins in the normal and malignant liver cells was indicated by 2-dimensional gel electrophoresis. Approximately 300 polypeptides were resolved by this technique. Most of these were quantitatively different in the normal and hepatoma nonhistone protein preparations. Several qualitative differences also seemed to be present. Nonhistone proteins from regenerating liver shared some polypeptides with hepatoma that were absent in normal liver. Nuclear proteins characteristic of malignant tissues may provide clues toward the understanding of gene regulation in malignant cells, and some of them could become useful tumor markers.