Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, P.R. China.
Int J Mol Med. 2010 Aug;26(2):273-9.
Hepatitis C virus (HCV) infection has become a severe health problem worldwide. The viral proteins are believed to be among the most important factors that contribute to HCV mediated pathogenesis. Accumulated evidence demonstrating that HCV non-structural protein 3 (NS3) possesses oncogenic potential, and is involved in the regulation of cell proliferation has been documented. In this study, we emphasized the effect of HCV NS3 protein on cell proliferation in the immortally normal hepatocyte QSG7701 cells. The cell line transfected with plasmid expressing NS3 protein showed enhanced cell growth, extracellular signal-related kinase (ERK) activation, DNA binding activities of transcription factors of activator protein 1 (AP-1) and NF-kappaB, and cyclin D1 overexpression, but without activation of Jun amino-terminal kinase or p38. Pre-treatment of NS3 protein expressing cells with ERK inhibitor, PD98059, blocked the activation of AP-1 and NF-kappaB, and inhibited cyclin D1 expression and cell proliferation. The results suggest that NS3-mediated cell growth occurs through activation of ERK/AP-1 and NF-kappaB/cyclin D1 cascades.
丙型肝炎病毒 (HCV) 感染已成为全球严重的健康问题。据信，病毒蛋白是导致 HCV 介导的发病机制的最重要因素之一。有大量证据表明，丙型肝炎非结构蛋白 3 (NS3) 具有致癌潜力，并参与细胞增殖的调节。在这项研究中，我们强调了 HCV NS3 蛋白对永生化正常肝细胞 QSG7701 细胞增殖的影响。转染表达 NS3 蛋白的质粒的细胞系显示出增强的细胞生长、细胞外信号相关激酶 (ERK) 激活、激活蛋白 1 (AP-1) 和 NF-κB 的转录因子的 DNA 结合活性以及细胞周期蛋白 D1 的过表达，但 Jun 氨基末端激酶或 p38 没有被激活。用 ERK 抑制剂 PD98059 预处理表达 NS3 蛋白的细胞，阻断了 AP-1 和 NF-κB 的激活，并抑制了细胞周期蛋白 D1 的表达和细胞增殖。结果表明，NS3 介导的细胞生长是通过 ERK/AP-1 和 NF-κB/细胞周期蛋白 D1 级联的激活发生的。
