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, 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.