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首页> 外文期刊>Cell Research >The involvement of XPC protein in the cisplatin DNA damaging treatment-mediated cellular response.
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The involvement of XPC protein in the cisplatin DNA damaging treatment-mediated cellular response.

机译：XPC蛋白参与顺铂DNA破坏治疗介导的细胞反应。

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Recognition of DNA damage is a critical step for DNA damage-mediated cellular response. XPC is an important DNA damage recognition protein involved in nucleotide excision repair (NER). We have studied the XPC protein in cisplatin DNA damaging treatment-mediated cellular response. Comparison of the microarray data from both normal and XPC-defective human fibroblasts identified 861 XPC-responsive genes in the cisplatin treatment (with minimum fold change>1.5). The cell cycle and cell proliferation-related genes are the most affected genes by the XPC defect in the treatment. Many other cellular function genes, especially the DNA repair and signal transduction-related genes, were also affected by the XPC defect in the treatment. To validate the microarray data, the transcription levels of some microarray-identified genes were also determined by an rt-PCR based real time PCR assay. The real time PCR results are consistent with the microarray data for most of the tested genes, indicating the reliability of the microarray data. To further validate the microarray data, the cisplatin treatment-mediated caspase-3 activation was also determined. The Western blot hybridization results indicate that the XPC defect greatly attenuates the cisplatin treatment-mediated Caspase-3 activation. We elucidated the role of p53 protein in the XPC protein DNA damage recognition-mediated signaling process. The XPC defect reduces the cisplatin treatment-mediated p53 response. These results suggest that the XPC protein plays an important role in the cisplatin treatment-mediated cellular response. It may also suggest a possible mechanism of cancer cell drug resistance.
机译：DNA损伤的识别是DNA损伤介导的细胞反应的关键步骤。 XPC是一种重要的DNA损伤识别蛋白，参与核苷酸切除修复（NER）。我们已经研究了顺铂DNA损伤治疗介导的细胞反应中的XPC蛋白。正常人和XPC缺陷人成纤维细胞的微阵列数据比较确定了顺铂治疗中的861个XPC反应基因（最小倍数变化> 1.5）。细胞周期和细胞增殖相关基因是在治疗中受XPC缺陷影响最大的基因。许多其他细胞功能基因，特别是与DNA修复和信号转导相关的基因，也受到治疗中XPC缺陷的影响。为了验证微阵列数据，还通过基于rt-PCR的实时PCR测定法确定了一些微阵列识别基因的转录水平。实时PCR结果与大多数测试基因的微阵列数据一致，表明微阵列数据的可靠性。为了进一步验证微阵列数据，还测定了顺铂治疗介导的caspase-3激活。蛋白质印迹杂交结果表明，XPC缺陷大大减弱了顺铂治疗介导的Caspase-3激活。我们阐明了p53蛋白在XPC蛋白DNA损伤识别介导的信号传导过程中的作用。 XPC缺陷降低了顺铂治疗介导的p53反应。这些结果表明，XPC蛋白在顺铂治疗介导的细胞反应中起重要作用。也可能暗示了癌细胞耐药的可能机制。

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