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

• Published in: Acta pharmacologica Sinica Vol. 32; no. 5; pp. 611 - 618
• Main Authors: Sun, Hong-zhi, Xu, Lin, Zhou, Bo, Zang, Wei-jin, Wu, Shu-fang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2011; Nature Publishing Group
• Subjects: 1-Phosphatidylinositol 3-kinase; 3T3 Cells; Animals; Binding Sites; Biomedical and Life Sciences; Biomedicine; Cell Line, Tumor; Cells, Cultured; Confocal microscopy; cyclin; cyclin D1; DNA, Ribosomal - metabolism; Fibroblasts - metabolism; Gene Silencing; Immunology; Immunoprecipitation; Insulin Receptor Substrate Proteins - genetics; Insulin Receptor Substrate Proteins - metabolism; Insulin receptors; Internal Medicine; IRS-2 protein; Medical Microbiology; Mice; Nuclear transport; Oncogene Protein pp60(v-src) - metabolism; Original; original-article; Pharmacology/Toxicology; Phosphatidylinositol 3-Kinases - metabolism; Promoter Regions, Genetic; Promoters; Receptor, IGF Type 1 - genetics; RNA, Small Interfering - administration & dosage; siRNA; siRNAs; src; Src protein; Transformation; Vaccine; 基因改造; 消耗; 胰岛素受体底物; 致癌; 诱导; cellular transformation; cyclin D1 promoter; RNA interference; nuclear translocation; insulin receptor substrate 2 (IRS-2); v-src; rDNA promoter
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2011.18

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.