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ABSTRACT: 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.
SUBMITTER: Sun HZ
PROVIDER: S-EPMC4002513 | biostudies-literature | 2011 May
REPOSITORIES: biostudies-literature
Sun Hong-zhi HZ Xu Lin L Zhou Bo B Zang Wei-jin WJ Wu Shu-fang SF
Acta pharmacologica Sinica 20110502 5
<h4>Aim</h4>To investigate the role of insulin receptor substrate 2 (IRS-2) in oncogenic transformation induced by v-src.<h4>Methods</h4>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.<h4>Results</h4>Depletion of IRS-2 inhibited R-/v-src ...[more]