Kubin T, Gohda E, Yamamoto I
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Biochem Mol Biol Int. 1995 Jun;36(2):393-400.
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.
p53肿瘤抑制基因是人类癌症中最常发生改变的基因。在此我们证明,编码一种细胞p53结合蛋白的mdm2基因的转录本在给予四氯化碳后1至3小时内,在大鼠肝脏中显著增加,在12小时达到峰值,并在48小时后恢复到基础水平。然而,部分肝切除术后肝脏mdm2 mRNA水平没有显著变化。这与两种手术操作后均增加的p53基因表达形成对比。注射四氯化碳后,C-myc转录本也迅速增加,在3小时达到最高水平。血清丙氨酸转氨酶活性在最初12小时内较低,在四氯化碳注射后24小时达到最高。这些结果表明,在细胞死亡开始之前mdm2基因在肝脏中的短暂表达更可能反映与坏死相关的事件,而不是与细胞增殖相关的事件。