The Runx genes:: lineage-specific oncogenes and tumor suppressors
The Runx genes:: lineage-specific oncogenes and tumor suppressors
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DOI：
10.1038/sj.onc.1207130
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发表时间：
2004-05-24
期刊：
影响因子：
8
通讯作者：
Neil, JC
中科院分区：
文献类型：
--
作者：
Cameron, ER;Neil, JC
Runx基因对简单的癌基因或肿瘤抑制基因的二元分类提出了挑战。有证据表明，三种哺乳动物Runx基因中的两种功能丧失会促进癌症，但以高度谱系限制的方式。在人类白血病中，RUNX1基因参与产生致癌融合蛋白的各种染色体易位事件，其中至少一些似乎作为正常基因产物的显性负抑制剂发挥作用。奇怪的是，越来越多的证据表明，结构完整的Runx基因在过度表达时也是致癌的。所有这三个鼠基因作为转录激活的逆转录病毒插入突变的目标，和Runx2的致癌潜力已被证实在转基因小鼠。此外，RUNX1基因通常在急性白血病病例中扩增或过表达。在阐明Runx基因的致癌作用的进展状态是本次审查的主题，我们得出了最近的观察结果在一个暂定的模型Runx失调对造血细胞分化的影响。我们认为，谱系特异性因素决定了Runx因子丢失或过度表达的致癌效应的敏感性。
The Runx genes present a challenge to the simple binary classification of cancer genes as oncogenes or tumor suppressors. There is evidence that loss of function of two of the three mammalian Runx genes promotes cancer, but in a highly lineage-restricted manner. In human leukemias, the RUNX1 gene is involved in various chromosomal translocation events that create oncogenic fusion proteins, at least some of which appear to function as dominant-negative inhibitors of the normal gene product. Paradoxically, evidence is mounting that structurally intact Runx genes are also oncogenic when overexpressed. All the three murine genes act as targets for transcriptional activation by retroviral insertional mutagenesis, and the oncogenic potential of Runx2 has been confirmed in transgenic mice. Moreover, the RUNX1 gene is often amplified or overexpressed in cases of acute leukemia. The state of progress in elucidating the oncogenic roles of the Runx genes is the subject of this review, and we draw together recent observations in a tentative model for the effects of Runx deregulation on hematopoietic cell differentiation. We suggest that lineage-specific factors determine the sensitivity to the oncogenic effects of loss or overexpression of Runx factors.