ASIA unversity:Item 310904400/4636
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    Title: Upregulation of IKKalpha/IKKbeta by integrin linked kinase is required for HER2/neu-induced NF-kappaB anti-apoptotic pathway
    Authors: Malino, K.;Day, C.-P.;Wang, S.-C.;Li, Y. M.;Mien-Chie Hung
    Keywords: HER2/neu;ILK;PI-3K;Akt;TNF-;antiapoptotic pathway;IKK
    Date: 2004
    Issue Date: 2009-11-27 13:57:10 (UTC+8)
    Publisher: Asia University
    Abstract: Constitutively active HER2/neu activates nuclear factor kappa-B (NF-B) in cells and induces their resistance to apoptotic stimuli such as tumor necrosis factor- (TNF-). Here, we show that integrin-linked kinase (ILK), the crucial signal transducer in the integrin pathway, is involved in HER2/neu-mediated activation of NF-B. Expression of HER2/neu increases ILK activity. Blocking ILK activity with a kinase-deficient mutant ILK (ILK-KD) inhibits NF-B activation and sensitizes HER2/neu-transformed cells to TNF--induced apoptosis. Stable expression of ILK-KD in HER2/neu-transformed cells suppressed Akt phosphorylation and the expression of IB kinase and (IKK and ) at both the protein and mRNA levels, preventing IB- degradation and NF-B activation. Furthermore, HER2/neu stimulated the transcriptional activity of the putative IKK promoter through ILK and Akt. Our results demonstrate that upregulation of IKK and IKK by the ILK/Akt pathway is required for the HER2/neu-mediated NF-B antiapoptotic pathway.
    Relation: ONCOGENE 23(21):3883-3887
    Appears in Collections:[Department of Biotechnology] Journal Article

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