Depletion of insulin receptor substrate 2 reverses 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, confoca...
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Published in | Acta pharmacologica Sinica Vol. 32; no. 5; pp. 611 - 618 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
01.05.2011
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | insulin receptor substrate 2 (IRS-2); cellular transformation; nuclear translocation; v-src; cyclin D1 promoter; rDNA promoter;RNA interference 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. 31-1347/R ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 These authors contributed equally to this work. |
ISSN: | 1671-4083 1745-7254 |
DOI: | 10.1038/aps.2011.18 |