Interaction between nuclear insulin receptor substrate-2 and NF-κB in IGF-1 induces response in breast cancer cells
Affiliations: Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710060, P.R. China. email@example.com
- Published online on: December 1, 2010 https://doi.org/10.3892/or_00001016
- Pages: 1541-1550
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...
This article is mentioned in:
Despite significant homology between IRS-1 and IRS-2, recent studies have revealed distinct functions for these adaptor proteins in regulating breast cancer progression. Thus far, most of the studies on breast cancer have focused upon IRS-1, the biological pattern of IRS-2 is limited. We demonstrated that depletion of endogenous IRS-2 by antisense strategies impaired cell proliferation after serum withdrawal, blunted PI3K/Akt and NF-κB activation in IGF-1 induced response in MCF-7 and BT-20 breast cancer cells. In addition, IGF-1 promote nuclear translocation of IRS-2 and NF-κB in MCF-7 and BT-20 cells. Nuclear IRS-2 interaction with NF-κB-p65 and PI3K binding tyrosine residues of IRS-2 are crucial for the NF-κB activities. Moreover, nuclear IRS-2 is recruited to the cyclin D1 promoter both in MCF-7 and BT-20 cells. The selective inhibition of NF-κB-65 abolished the occupancy of IRS-2 to the cyclin D1 promoters. Our studies suggest that IRS-2 plays a significant role by activating, at least in part, NF-κB via PI3K/Akt pathway in IGF-1-induced responses in breast cancer cells and the crosstalk between nuclear IRS-2 and NF-κB might be responsible for transcriptional progression of the breast cancer cells.