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The Role of NF-κB in Hepatitis B Virus X Protein-Mediated Upregulation of VEGF and MMPs

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单位: [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Hepat Surg Ctr, Tongji Hosp, Wuhan, Hubei, Peoples R China
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关键词: Carcinogenesis Invesion & metastais Tumor cell biology Liver & billary system cancer

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Hepatitis B virus X protein (HBx) promotes hepatocellular carcinoma (HCC) invasion and metastasis by a poorly understood mechanism. This study investigated the role of NF-kappa B in HBx-mediated upregulation of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). In a stably expressing HBx cell line, NF-kappa B level was examined by laser scanning confocal microscopy before and after treatment with pyrrolidine dithiocarbamate (PDTC; an NF-kappa B inhibitor). VEGF, MMP2, MMP9, and MMP14 mRNA and protein levels were quantitated by real-time PCR and Western blotting, respectively. HBx stimulated NF-kappa B signaling and increased VEGF, MMP2, MMP9, and MMP14 mRNA and protein levels. PDTC treatment blocked HBx-mediated stimulation of NF-kappa B signaling and decreased VEGF, MMP9, and MMP14 (but not MMP2) mRNA and protein levels. In vivo studies, PDTC reduced angiogenesis in subcutaneous xenograft of nude mice which injected HepG2-HBx cells. This suggests that NF-kappa B is involved in upregulating these genes and in the HBx-mediated invasion and metastasis of HCC.

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出版当年[2009]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
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出版当年[2008]版:
Q3 ONCOLOGY
最新[2024]版:
Q3 ONCOLOGY

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第一作者单位: [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Hepat Surg Ctr, Tongji Hosp, Wuhan, Hubei, Peoples R China
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