To elucidate cell differentiation in liver carcinogenesis, we have stu
died the CCAAT/enhancer-binding protein (C/EBP). C/EBP is a positive-a
cting transcription factor important for the maintenance of liver-spec
ific functions. It is associated with differentiation and regarded as
an anti-proliferative agent. We have studied the expression and locali
zation of C/EBP during sequential rat liver carcinogenesis. Two-color
immunohistochemistry and confocal laser scan microscopy demonstrated C
/EBP in hepatocyte nuclei and preneoplastic liver lesions, but not in
bile ducts, non-parenchymal cells or oval cells. Both western blotting
and immunohistochemistry revealed down-regulation of C/EBP during nor
mal regeneration and when regeneration was inhibited by the carcinogen
, 2-acetylaminofluorene. A similar down-regulation was shown by wester
n blotting in hepatocytes grown in culture. Our data suggest that the
altered metabolic phenotype of preneoplastic liver lesions was not cau
sed by a change in the expression of C/EBP. Furthermore, the data favo
r a hepatocyte derivation of preneoplastic liver lesions.