Interaction between nuclear insulin receptor substrate-2 and NF-κB in IGF-1 induces response in breast cancer cells

  • Authors:
    • Shufang Wu
    • Bo Zhou
    • Lin Xu
    • Hongzhi Sun
  • View Affiliations

  • Published online on: December 1, 2010     https://doi.org/10.3892/or_00001016
  • Pages: 1541-1550
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Abstract

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.

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December 2010
Volume 24 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Wu S, Zhou B, Xu L and Sun H: Interaction between nuclear insulin receptor substrate-2 and NF-κB in IGF-1 induces response in breast cancer cells . Oncol Rep 24: 1541-1550, 2010.
APA
Wu, S., Zhou, B., Xu, L., & Sun, H. (2010). Interaction between nuclear insulin receptor substrate-2 and NF-κB in IGF-1 induces response in breast cancer cells . Oncology Reports, 24, 1541-1550. https://doi.org/10.3892/or_00001016
MLA
Wu, S., Zhou, B., Xu, L., Sun, H."Interaction between nuclear insulin receptor substrate-2 and NF-κB in IGF-1 induces response in breast cancer cells ". Oncology Reports 24.6 (2010): 1541-1550.
Chicago
Wu, S., Zhou, B., Xu, L., Sun, H."Interaction between nuclear insulin receptor substrate-2 and NF-κB in IGF-1 induces response in breast cancer cells ". Oncology Reports 24, no. 6 (2010): 1541-1550. https://doi.org/10.3892/or_00001016