Activation of NF-kappa B, AP-1 and STAT transcription factors is a frequent and early event in human hepatocellular carcinomas.
OBJECTIVE
Hepatitis B and C viruses, two inducers of hepatocarcinomas, have been shown to activate AP-1, NF-kappa B and STAT in vitro, but no detailed information on the activity of these transcription factors in vivo have been provided.


METHODS
We have measured the DNA binding activity of these transcription factors in the peri-tumoral and the tumoral parts of 15 primary liver cancers, of viral or non-viral etiologies, and in five hepatic metastases using electrophoretic mobility shift assays.


RESULTS
AP-1, NF-kappa B and STAT binding activities were increased in the peritumoral tissue, compared with histologically normal livers in 73, 87 and 70%, respectively, of the cases. A further activation of AP-1, NF-kappa B, but not STAT binding in the tumoral parts was detected in 40 and 80%, respectively, of the cases. A close correlation was found between JunD and c-Jun levels and AP-1 binding activity at the tumoral stage. By contrast, AP-1 and NF-kappa B binding activities were low or only slightly elevated in the peri-tumoral and the tumoral tissue of metastases.


CONCLUSIONS
Early activation of AP-1, NF-kappa B and STAT contributes probably to the acquisition of a transformed phenotype during hepatocarcinogenesis, whatever the etiology.
Liu
Ping
P
Laboratoire de Biologie Cellulaire, INSERM U 327, Faculté de Médecine Xavier Bichat, 16 rue Henri Huchard, 75018 Paris, France.
Kimmoun
Elisabeth
E
Legrand
Agnès
A
Sauvanet
Alain
A
Degott
Claude
C
Lardeux
Bernard
B
Bernuau
Dominique
D
D006528:Carcinoma, Hepatocellular / Q000503:physiopathology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000503:physiopathology*; D016328:NF-kappa B / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D018808:Transcription Factor AP-1