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.
| Original language | English |
|---|---|
| Pages (from-to) | 611-618 |
| Number of pages | 8 |
| Journal | Acta Pharmacologica Sinica |
| Volume | 32 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2011 |
Keywords
- RNA interference
- cellular transformation
- cyclin D1 promoter
- insulin receptor substrate 2 (IRS-2)
- nuclear translocation
- rDNA promoter
- v-src