Expression of the protooncogene mdm2 markedly increases in response to carbon tetrachloride but not after partial hepatectomy in contrast to p53.
The p53 tumor-suppressor gene is the most commonly altered gene in human cancers. Here we demonstrate that transcripts of the mdm2 gene, which encodes a cellular p53 binding protein, markedly increased in the rat liver within 1 to 3 h, reached a peak at 12 h and returned to the basal level 48 h after the administration of carbon tetrachloride. However, the level of hepatic mdm2 mRNA did not significantly change after partial hepatectomy. This is in contrast to p53 gene expression which increased after either procedure. C-myc transcripts also rapidly increased after the injection of carbon tetrachloride, reaching a maximal level at 3 h. The activity of serum alanine aminotransferase was low within the first 12 h and was maximal 24 h after carbon tetrachloride. These results suggest that the transient hepatic expression of the mdm2 gene prior to the onset of cell death is more likely to reflect events associated with necrosis rather than with cell proliferation.
Kubin
T
T
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Gohda
E
E
Yamamoto
I
I
D000410:Alanine Transaminase / Q000097:blood; D000595:Amino Acid Sequence; D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D002478:Cells, Cultured; D015342:DNA Probes; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D016158:Genes, p53; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D015342:DNA Probes; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D002251:Carbon Tetrachloride; C497208:Mdm2 protein, rat; D051736:Proto-Oncogene Proteins c-mdm2; D000410:Alanine Transaminase