Depletion of insulin receptor substrate 2 reverses oncogenic transformation induced by v-src  

作　　者：Hong-zhi SUN Lin XU Bo ZHOU Wei-jin ZANG Shu-fang WU 

机构地区：[1]Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Medical School of Xi'an Jiaotong University, Xi'an 710061, China

出　　处：《Acta Pharmacologica Sinica》2011年第5期611-618,共8页中国药理学报（英文版）

基　　金：Acknowledgements We are grateful for the donation of plasmids from Dr Renato BASERGA at the Kimmel Cancer Center. This work was supported by grants from the National Natural Science Foundation of China （Key Program, No 30930105; General Program, No 30971392） and the National Basic Research Program of China （973 Program, No 2007CB512005）. This work was also supported by the New Century Excellent Talent in University from the Ministry of Education program （NCET-08-0435） and the ＂Tengfei＂ Supporting Program of Xi＇an Jiaotong University.

摘　　要：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.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.

关 键 词：insulin receptor substrate 2 （IRS-2） cellular transformation nuclear translocation V-SRC cyclin D1 promoter rDNA promoter RNA interference 

分 类 号：Q578[生物学—生物化学] S188[农业科学—农业基础科学]