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首页> 外文期刊>Molecular biology reports >Amplification and overexpression of oncogene Mdm2 and orphan receptor gene Nr1h4 in immortal PRKDC knockout cells
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Amplification and overexpression of oncogene Mdm2 and orphan receptor gene Nr1h4 in immortal PRKDC knockout cells

机译:永生PRKDC基因敲除细胞中癌基因Mdm2和孤儿受体基因Nr1h4的扩增和过表达

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摘要

DNA-dependent protein kinase (DNA-PK) is required for the repair of double strand DNA breaks by nonhomologous DNA end joining. The catalytic subunit of DNA-PK, PRKDC, may also be involved in repair-related or separate cell signaling pathways. To learn more about the cellular function of DNA-PK under normal physiological conditions, we identified genes that are differentially expressed between an immortalized wild-type mouse fibroblast cell line and its DNA-PK-deficient counterpart (Prkdc -/-). The proto-oncogene Mdm2 and the farnesoid X receptor gene Nr1h4 were overexpressed in the DNA-PK-deficient cell line. We show that in the DNA-PK-deficient cell line the genes for both Mdm2 and Nr1h4 are amplified to a degree that could account for most, if not all, of their increased expression. Other genes were strongly downregulated in the DNA-PK-deficient cell line, but this opposite expression pattern was not due to gene amplification in the wild-type cells. None of these genes was differentially expressed in DNA-PK-containing and DNA-PK-deficient primary mouse embryo fibroblasts. Our results suggest a model in which DNA-PK indirectly affects the cellular gene expression profile through its caretaker role and by preventing gene amplification.
机译:DNA依赖性蛋白激酶(DNA-PK)是通过非同源DNA末端连接修复双链DNA断裂所必需的。 DNA-PK的催化亚基PRKDC也可能参与修复相关或独立的细胞信号通路。要了解有关正常生理条件下DNA-PK细胞功能的更多信息,我们鉴定了永生化野生型小鼠成纤维细胞系及其DNA-PK缺陷对应物(Prkdc-/-)之间差异表达的基因。原癌基因Mdm2和法呢类X受体基因Nr1h4在DNA-PK缺陷细胞系中过表达。我们表明,在DNA-PK缺陷型细胞系中,Mdm2和Nr1h4的基因都被扩增到一定程度,这可能解释了大部分(如果不是全部)它们表达的增加。其他基因在DNA-PK缺陷型细胞系中被强烈下调,但是这种相反的表达方式不是由于野生型细胞中的基因扩增。这些基因均未在含有DNA-PK和缺乏DNA-PK的原代小鼠胚胎成纤维细胞中差异表达。我们的结果提出了一种模型,其中DNA-PK通过其看护角色并通过防止基因扩增间接影响细胞基因表达谱。

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