title: HER-2-induced PI3K signaling pathway was involved in the pathogenesis of gastric cancer.
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.
authors.affiliation: The Third Xiang-Ya Hospital, Central South University, Changsha, China.
authors.forename: Y F
authors.initials: YF
authors.lastname: Fu
authors.affiliation: The Third Xiang-Ya Hospital, Central South University, Changsha, China.
authors.forename: R
authors.initials: R
authors.lastname: Gui
authors.affiliation: The Third Xiang-Ya Hospital, Central South University, Changsha, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D034622:RNA Interference; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019139:Tumor Escape; D015854:Up-Regulation
chemical_list: D018799:Intercellular Adhesion Molecule-1; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human