...
首页> 外文期刊>Oncogene >Inhibitory effect of c-Myc on p53-induced apoptosis in leukemia cells. Microarray analysis reveals defective induction of p53 target genes and upregulation of chaperone genes
【24h】

Inhibitory effect of c-Myc on p53-induced apoptosis in leukemia cells. Microarray analysis reveals defective induction of p53 target genes and upregulation of chaperone genes

机译:c-Myc对p53诱导的白血病细胞凋亡的抑制作用。基因芯片分析揭示了p53靶基因的诱导缺陷和伴侣基因的上调

获取原文
           

摘要

We have previously demonstrated that c-Myc impairs p53-mediated apoptosis in K562 human leukemia cells, which lack ARF. To investigate the mechanisms by which c-Myc protects from p53-mediated apoptosis, we used K562 cells that conditionally express c-Myc and harbor a temperature-sensitive allele of p53. Gene expression profiles of cells expressing wild-type conformation p53 in the presence of either uninduced or induced c-Myc were analysed by cDNA microarrays. The results show that multiple p53 target genes are downregulated when c-Myc is present, including p21WAF1, MDM2, PERP, NOXA, GADD45, DDB2, PIR121 and p53R2. Also, a number of genes that are upregulated by c-Myc in cells expressing wild-type conformation p53 encode chaperones related to cell death protection as HSP105, HSP90 and HSP27. Both downregulation of p53 target genes and upregulation of chaperones could explain the inhibition of apoptosis observed in K562 cells with ectopic c-Myc. Myc-mediated impairment of p53 transactivation was not restricted to K562 cells, but it was reproduced in a panel of human cancer cell lines derived from different tissues. Our data suggest that elevated levels of Myc counteract p53 activity in human tumor cells that lack ARF. This mechanism could contribute to explain the c-Myc deregulation frequently found in cancer.
机译:先前我们已经证明c-Myc会损害缺乏ARF的K562人白血病细胞中p53介导的凋亡。为了研究c-Myc保护免受p53介导的细胞凋亡的机制,我们使用了有条件表达c-Myc并包含p53温度敏感等位基因的K562细胞。通过cDNA微阵列分析在未诱导或诱导的c-Myc存在下表达野生型构象p53的细胞的基因表达谱。结果显示,当存在c-Myc时,多个p53靶基因被下调,包括p21WAF1,MDM2,PERP,NOXA,GADD45,DDB2,PIR121和p53R2。同样,在表达野生型构象p53的细胞中,许多由c-Myc上调的基因编码与细胞死亡保护相关的伴侣蛋白,如HSP105,HSP90和HSP27。 p53靶基因的下调和分子伴侣的上调都可以解释在异位c-Myc对K562细胞凋亡的抑制作用。 Myc介导的p53反式激活的损害不仅限于K562细胞,而且在一组衍生自不同组织的人类癌细胞系中得以复制。我们的数据表明,升高水平的Myc会抵消缺乏ARF的人类肿瘤细胞中p53的活性。这种机制可能有助于解释癌症中常见的c-Myc失调。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号