Overexpression of Mdm2 in mice reveals a p53-independent role for Mdm2 in tumorigenesis
Overexpression of Mdm2 in mice reveals a p53-independent role for Mdm2 in tumorigenesis
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DOI：
10.1073/pnas.95.26.15608
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发表时间：
1998-12-22
影响因子：
11.1
通讯作者：
Bradley, A
中科院分区：
文献类型：
--
作者：
Jones, SN;Hancock, AR;Bradley, A
Mdm2原癌基因在人类肉瘤中扩增到高拷贝数，并在多种其他人类癌症中过表达。由于Mdm 2蛋白与p53肿瘤抑制蛋白形成复合物并下调p53功能，因此推测Mdm 2的致癌潜力是p53依赖性的。为了在小鼠中模拟这些条件，我们使用了整个Mdm 2基因，在其天然启动子区域的转录控制下，作为转基因来创建过表达Mdm 2的小鼠。转基因小鼠易自发形成肿瘤，并且在存在或不存在功能性p53的情况下在Mdm 2转基因小鼠中观察到的肉瘤的发生率表明，除了Mdm 2介导的p53失活之外，Mdm 2在肿瘤发生中存在p53非依赖性作用。
The Mdm2 proto-oncogene is amplified to high copy numbers in human sarcomas and is overexpressed in a wide variety of other human cancers. Because Mdm2 protein forms a complex with the p53 tumor suppressor protein and down-regulates p53 function, the oncogenic potential of Mdm2 is presumed to be p53-dependent. To model these conditions in mice, we have used the entire Mdm2 gene, under transcriptional control of its native promoter region, as a transgene to create mice that overexpress Mdm2. The transgenic mice are predisposed to spontaneous tumor formation, and the incidence of sarcomas observed in the Mdm2-transgenic mice in the presence or absence of functional p53 demonstrates that, in addition to Mdm2-mediated inactivation of p53, there exists a p53-independent role for Mdm2 in tumorigenesis.