title: Depletion of insulin receptor substrate 2 reverses oncogenic transformation induced by v-src.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Depletion of insulin receptor substrate 2 could reverse oncogenic transformation induced by v-src.
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Medical School of Xi'an Jiaotong University, Xi'an 710061, China. sunhongzhi@mail.xjtu.edu.cn
authors.forename: Hong-zhi
authors.initials: HZ
authors.lastname: Sun
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.forename: Wei-jin
authors.initials: WJ
authors.lastname: Zang
authors.forename: Shu-fang
authors.initials: SF
authors.lastname: Wu
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004275:DNA, Ribosomal / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D020868:Gene Silencing; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000008:administration & dosage; D017526:Receptor, IGF Type 1 / Q000235:genetics
chemical_list: D004275:DNA, Ribosomal; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; C526298:Irs2 protein, mouse; D034741:RNA, Small Interfering; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D015688:Oncogene Protein pp60(v-src)