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Wu, Shufang (Wu, Shufang.) (Scholars:武淑芳) | Zhou, Bo (Zhou, Bo.) | Xu, Lin (Xu, Lin.) | Sun, Hongzhi (Sun, Hongzhi.)

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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-kappa B 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-kappa B in MCF-7 and BT-20 cells. Nuclear IRS-2 interaction with NF-kappa B-p65 and PI3K binding tyrosine residues of IRS-2 are crucial for the NF-kappa B 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-kappa B-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-kappa B via PI3K/Akt pathway in IGF-1-induced responses in breast cancer cells and the crosstalk between nuclear IRS-2 and NF-kappa B might be responsible for transcriptional progression of the breast cancer cells.


IRS-2 breast cancer cells NF-kappa B cyclin D1 promoters IGF-1 induced response

Author Community:

  • [ 1 ] [Wu, Shufang; Zhou, Bo; Xu, Lin; Sun, Hongzhi] Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 1, Key Lab Environm & Genes Related Dis,Minist Educ, Xian 710060, Peoples R China

Reprint Author's Address:

  • Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 1, Key Lab Environm & Genes Related Dis,Minist Educ, Xian 710060, Peoples R China.

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ISSN: 1021-335X

Year: 2010

Issue: 6

Volume: 24

Page: 1541-1550

1 . 6 8 6


3 . 0 4 1



ESI HC Threshold:197

JCR Journal Grade:3

CAS Journal Grade:4

Cited Count:

WoS CC Cited Count: 6

SCOPUS Cited Count:

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 11

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