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HER-2-induced PI3K signaling pathway was involved in the pathogenesis of gastric cancer

Cancer Gene Therapy volume 22, pages 145–153 (2015)Cite this article

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Abstract

Human epidermal growth factor receptor-2 (HER-2) overexpression was closely associated with the tumor growth and invasion, we here aimed to investigate the mechanism of HER-2 mediation in the pathogenesis of gastric cancer (GC). We first detected the expression of HER-2 in GC cell line SGC-7901 and then examined the levels of nuclear factor-κB (NF-κB), matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) and the association between them by molecular methods. Statistical analysis was used to compare the significance. We further detected the possible molecular mechanism involved in their relationship in the SGC-7901 genesis. The MMP-9, NF-κB and secretory type (s-ICAM-1) levels were significantly greater in peripheral blood serum from SGC-7901 than healthy control GES-1 (P<0.01). ICAM-1, MMP-9 and NF-κB mRNA and protein levels were more highly expressed in SGC-7901 than healthy control GES-1. The expression levels of NF-κB, MMP-9 and ICAM-1 were positively related in GC cell line SGC-7901, which was HER-2 positive. The HER-2 positive SGC-7901 secreted more transforming growth factor beta 1 (TGF-β1) and resultantly activated MMP-9 to enhance s-ICAM-1 secretion and further studies showed that phosphatidylinositol-3 kinase (PI3K)/Akt/NF-κB signaling pathway was involved in GC pathogenesis. The GC cells that express the HER-2 oncogene spur the activation of NF-κB that can upregulate the expression of ICAM-1 and induce the expression of MMP-9, which hydrolyzes ICAM-1 into s-ICAM-1 to promote tumor immune escape. TGF-β1-induced PI3K/Akt/NF-κB signaling pathway was involved in the pathogenesis of GC and they could be a new target for cancer therapy. The GC cells that express the HER-2 oncogene spur the activation of NF-κB that can upregulate the expression of ICAM-1 and induce the expression of MMP-9, which hydrolyzes ICAM-1 into s-ICAM-1 to promote tumor immune escape. TGF-β1-induced PI3K/Akt/NF-κB signaling pathway was involved in the pathogenesis of GC and they could be a new target for cancer therapy.

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Authors and Affiliations

  1. The Third Xiang-Ya Hospital, Central South University, Changsha, China

    Y F Fu, R Gui & J Liu

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Correspondence to Y F Fu.

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Fu, Y., Gui, R. & Liu, J. HER-2-induced PI3K signaling pathway was involved in the pathogenesis of gastric cancer. Cancer Gene Ther 22, 145–153 (2015). https://doi.org/10.1038/cgt.2014.80

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