CCAAT/enhancer-binding protein (C/EBP) immunoreactivity during rat liver carcinogenesis.
To elucidate cell differentiation in liver carcinogenesis, we have studied the CCAAT/enhancer-binding protein (C/EBP). C/EBP is a positive-acting transcription factor important for the maintenance of liver-specific functions. It is associated with differentiation and regarded as an anti-proliferative agent. We have studied the expression and localization 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 normal regeneration and when regeneration was inhibited by the carcinogen, 2-acetylaminofluorene. A similar down-regulation was shown by western blotting in hepatocytes grown in culture. Our data suggest that the altered metabolic phenotype of preneoplastic liver lesions was not caused by a change in the expression of C/EBP. Furthermore, the data favor a hepatocyte derivation of preneoplastic liver lesions.
Skarpen
E
E
Laboratory for Toxicopathology, National Hospital (Rikshospitalet), University of Oslo, Norway.
Lindeman
B
B
Thoresen
G H
GH
Låg
M
M
Christoffersen
T
T
Huitfeldt
H S
HS
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins; D002273:Carcinogens / Q000494:pharmacology; D002469:Cell Separation; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D004742:Enhancer Elements, Genetic; D019085:Fluorescent Antibody Technique, Direct; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology; D008297:Male; D018613:Microscopy, Confocal; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D002273:Carcinogens; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D015073:2-Acetylaminofluorene