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首页> 外文期刊>Oncogene >Overexpression of mammalian Rad51 does not stimulate tumorigenesis while a dominant-negative Rad51 affects centrosome fragmentation, ploidy and stimulates tumorigenesis, in p53-defective CHO cells
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Overexpression of mammalian Rad51 does not stimulate tumorigenesis while a dominant-negative Rad51 affects centrosome fragmentation, ploidy and stimulates tumorigenesis, in p53-defective CHO cells

机译：在p53缺陷的CHO细胞中，哺乳动物Rad51的过表达不会刺激肿瘤发生，而显性阴性的Rad51影响中心体片段化，倍性并刺激肿瘤发生。

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摘要

Rad51 protein plays a pivotal role in homologous recombination (HR), which is involved in double-strand break repair and in genome maintenance. Despite interactions with tumor suppressor proteins, the role of mammalian Rad51 and more generally of HR in tumor prevention is not clearly established. Indeed, both high and low frequencies of HR as well as high and low levels of RAD51 expression have been reported in tumors and in precancerous conditions. To address the question of the impact of HR on tumorigenesis, we used Chinese hamster ovary (CHO) p53-defective cell lines overexpressing the mouse MmRAD51, which stimulates HR (we name these lines: Hyper-rec lines). In parallel, we used CHO cell lines expressing a RAD51 dominant-negative form that specifically inhibits gene conversion without affecting cell viability (Hypo-rec lines). These different lines were injected into nude mice to measure their tumorigenicity. Hypo-rec lines generated a higher frequency of tumors, which also exhibited faster growth, compared to control and Hyper-rec lines. Consistent with tumorigenicity, Hypo-rec cells exhibit spontaneous centrosome duplication defects and aneuploidy. These results are the first direct evidence of involvement of RAD51 in tumor repression.
机译：Rad51蛋白在同源重组（HR）中起着关键作用，同源重组涉及双链断裂修复和基因组维护。尽管与肿瘤抑制蛋白有相互作用，但哺乳动物Rad51和更普遍的HR在肿瘤预防中的作用尚不清楚。实际上，在肿瘤和癌前状态中已经报道了HR的高频率和低频率以及RAD51表达的高和低水平。为了解决HR对肿瘤发生的影响，我们使用了过度表达小鼠MmRAD51的中国仓鼠卵巢（CHO）p53缺陷细胞系，该细胞系刺激HR（我们将其命名为Hyper-rec系）。平行地，我们使用表达RAD51显性-阴性形式的CHO细胞系，其特异性抑制基因转化而不影响细胞活力（Hypo-rec系）。将这些不同的系注射到裸鼠中以测量其致瘤性。与对照和Hyper-rec品系相比，Hypo-rec品系产生更高频率的肿瘤，并且还表现出更快的生长。与致瘤性一致，Hypo-rec细胞表现出自发的中心体复制缺陷和非整倍性。这些结果是RAD51参与肿瘤抑制的第一个直接证据。

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