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

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 p

SUBMITTER: Sun HZ 

PROVIDER: S-EPMC4002513 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature