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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A Panel Of Isogenic Human Cancer Cells Suggests A Therapeutic Approach For Cancers With Inactivated P53
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A Panel Of Isogenic Human Cancer Cells Suggests A Therapeutic Approach For Cancers With Inactivated P53

机译：一组同基因的人类癌细胞建议用于P53灭活的癌症的治疗方法

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Through targeted homologous recombination, we developed a panel of matched colorectal cancer cell lines that differ only with respect to their endogenous TP53 status. We then used these lines to define the genes whose expression was altered after DNA damage induced by ionizing radiation. Transcriptome analyses revealed a consistent up-regulation of polo-like kinase 1 (PLK1) as well as other genes controlling the G_2/M transition in the cells whose TPS3 genes were inactivated compared with those with WT TP53 genes. This led to the hypothesis that the viability of stressed cells without WT TP53 depended on PLK1. This hypothesis was validated by demonstrating that stressed cancer cells without WT TPS3 alleles were highly sensitive to PLK1 inhibitors, both in vivo and in vitro.
机译：通过有针对性的同源重组，我们开发了一组匹配的结肠直肠癌细胞系，这些细胞系仅在其内源性TP53状态方面有所不同。然后，我们用这些谱线定义了在电离辐射诱导的DNA损伤后其表达发生改变的基因。转录组分析显示，与带有WT TP53基因的细胞相比，TPS3基因失活的细胞中polo样激酶1（PLK1）以及其他控制G_2 / M过渡的基因具有一致的上调。这导致了这样一个假设：没有WT TP53的应激细胞的活力取决于PLK1。通过证明没有WT TPS3等位基因的应激癌细胞在体内和体外均对PLK1抑制剂高度敏感，从而验证了这一假设。

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