Ohnishi T, Wang X, Ohnishi K, Takahashi A
Department of Biology, Nara Medical University, Kashihara, Japan.
Oncogene. 1998 Mar;16(11):1507-11. doi: 10.1038/sj.onc.1201663.
Induction of WAF1 expression was investigated in human glioblastoma cell lines differing in p53 gene statuses after cold shock treatment. Accumulation of both wild-type (wt) and mutant p53 (mp53) was induced by cold shock at 4 degrees C for 60 min, however, WAF1 accumulation was induced by cold shock in A-172 cells carrying the wtp53 but not in T98G cells carrying the mp53. Inactivation of wtp53 by a dominant negative p53 mutant (p53Trp248) abolished cold shock-induced WAF1 expression in A-172 transfectant cells. Furthermore, no WAF1 expression was induced by cold shock in p53-deficient human osteosarcoma Saos-2 cells. Northern blot analysis showed that the WAF1 but not p53 gene was activated by cold shock only in A-172 cells. These findings suggest that WAF1 expression is cold shock-inducible in human glioblastoma cells, and that this induction may be due to signal transduction mediated by p53 in response to non-genotoxic stress, cold shock.
在冷休克处理后，对p53基因状态不同的人胶质母细胞瘤细胞系中WAF1表达的诱导情况进行了研究。野生型（wt）和突变型p53（mp53）在4℃冷休克60分钟后均被诱导积累，然而，携带wtp53的A-172细胞中冷休克可诱导WAF1积累，而携带mp53的T98G细胞中则不然。显性负性p53突变体（p53Trp248）使wtp53失活，消除了A-172转染细胞中冷休克诱导的WAF1表达。此外，p53缺陷的人骨肉瘤Saos-2细胞经冷休克未诱导出WAF1表达。Northern印迹分析表明，仅在A-172细胞中冷休克可激活WAF1基因而非p53基因。这些发现提示，WAF1表达在人胶质母细胞瘤细胞中可被冷休克诱导，且这种诱导可能是由于p53介导的信号转导对非基因毒性应激——冷休克的反应所致。
