胰岛素受体底物 2 的耗竭逆转了 v-src 诱导的致癌转化。
Depletion of insulin receptor substrate 2 reverses oncogenic transformation induced by v-src.
机构信息
Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Medical School of Xi'an Jiaotong University, Xi'an 710061, China.
出版信息
Acta Pharmacol Sin. 2011 May;32(5):611-8. doi: 10.1038/aps.2011.18. Epub 2011 May 2.
AIM
To investigate the role of insulin receptor substrate 2 (IRS-2) in oncogenic transformation induced by v-src.
METHODS
IRS-2 gene was silenced using small interfering RNAs (siRNAs). Nuclear translocation and interaction of IRS-2 with v-src was determined using subcellular fractionation, confocal microscopy, and immunoprecipitation. The activity of the cyclin D1 promoter and r-DNA promoter was measured with a luciferase assay.
RESULTS
Depletion of IRS-2 inhibited R-/v-src cell growth and reverse the oncogenic transformation. IRS-2 bound to src via its two PI3-K binding sites, which are critical for activities involved in the transformation. Nuclear IRS-2 occupied the cyclin D1 and rDNA promoters. The combination of IRS-2 and v-src increased the activity of the two promoters, especially the rDNA promoter.
CONCLUSION
Depletion of insulin receptor substrate 2 could reverse oncogenic transformation induced by v-src.
目的
研究胰岛素受体底物 2（IRS-2）在 v-src 诱导的致癌转化中的作用。
方法
使用小干扰 RNA（siRNA）沉默 IRS-2 基因。使用亚细胞分级分离、共聚焦显微镜和免疫沉淀来确定 IRS-2 与 v-src 的核易位和相互作用。通过荧光素酶测定法测量细胞周期蛋白 D1 启动子和 r-DNA 启动子的活性。
结果
IRS-2 的耗竭抑制了 R-/v-src 细胞的生长并逆转了致癌转化。IRS-2 通过其两个 PI3-K 结合位点与 src 结合，这对于参与转化的活性至关重要。核 IRS-2 占据了细胞周期蛋白 D1 和 rDNA 启动子。IRS-2 和 v-src 的结合增加了两个启动子的活性，特别是 rDNA 启动子的活性。
结论
IRS-2 的耗竭可以逆转 v-src 诱导的致癌转化。
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