Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1
Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1
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DOI：
10.1038/ng1635
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发表时间：
2005-10-01
期刊：
影响因子：
30.8
通讯作者：
Hunter, KW
中科院分区：
文献类型：
--
作者：
Park, YG;Zhao, XH;Hunter, KW
我们以前确定了小鼠基因组中的基因座，这些基因座对乳腺肿瘤的转移效率有很大影响。在这里，我们提出的数据支持的想法，信号转导分子，Sipa 1，是潜在的转移效率修饰基因座Mtes 1的候选人。候选基因的分析确定了影响Sipa 1 Rap-GAP功能的Sipa 1非同义氨基酸多态性。使用异位表达Sipa 1的细胞或敲低Sipa 1表达的细胞进行的自发转移试验表明，转移能力与细胞Sipa 1水平相关。我们检查了人类表达数据，发现它们与Sipa 1浓度在转移中起作用的想法一致。综上所述，这些数据表明Sipa 1多态性是Mtes 1基因座的遗传多态性之一。据我们所知，这份报告也是第一次证明影响肿瘤转移的宪法遗传多态性。
We previously identified loci in the mouse genome that substantially influence the metastatic efficiency of mammary tumors. Here, we present data supporting the idea that the signal transduction molecule, Sipa1, is a candidate for underlying the metastasis efficiency modifier locus Mtes1. Analysis of candidate genes identified a nonsynonymous amino acid polymorphism in Sipa1 that affects the Sipa1 Rap-GAP function. Spontaneous metastasis assays using cells ectopically expressing Sipa1 or cells with knocked-down Sipa1 expression showed that metastatic capacity was correlated with cellular Sipa1 levels. We examined human expression data and found that they were consistent with the idea that Sipa1 concentration has a role in metastasis. Taken together, these data suggest that the Sipa1 polymorphism is one of the genetic polymorphisms underlying the Mtes1 locus. This report is also the first demonstration, to our knowledge, of a constitutional genetic polymorphism affecting tumor metastasis.