TAILIEUCHUNG - Báo cáo khoa học: " Hepatitis B virus X protein upregulates HSP90alpha expression via activation of c-Myc in human hepatocarcinoma cell line, HepG2"

Hepatitis B virus X protein upregulates HSP90alpha expression via activation of c-Myc in human hepatocarcinoma cell line, HepG2 | Li et al. Virology Journal 2010 7 45 http content 7 1 45 VIROLOGY JOURNAL RESEARCH Open Access Hepatitis B virus X protein upregulates HSP90alpha expression via activation of c-Myc in human hepatocarcinoma cell line HepG2 Weihua Li1 Xiaohui Miao2 Zhongtian Qi3 Wenting Zeng1 Jianxin Liang1 Zengwei Liang1 Abstract Background The Hepatitis B Virus X protein HBx plays a major role in hepatocellular carcinoma HCC development however its contribution to tumor invasion and metastasis has not been established so far. Heat shock protein 90 alpha HSP90alpha isoform is an ATP-dependent molecular chaperone that maintains the active conformation of client oncoproteins in cancer cells which is abundantly expressed in HCC especially in hepatitis B virus HBV -related tumors might be involved in tumor progression. Methods The levels of HSP90alpha extracellular signal-regulated kinase 1 2 ERK1 2 phosphorylated ERK1 2 p-ERK1 2 and c-Myc in HBx-transfected HepG2 cells were determined by western blots analysis. The endogenous ERKs activity was demonstrated by ELISA assay. The regulation of c-Myc-mediated HSP90 alpha promoter transactivation by HBx was evaluated through electrophoretic mobility shift analysis EMSA . The c-Myc-mediated HSP90alpha transcription was analysed by promoter assay. The HBx-expressing cells were transfected with specific small interference RNA siRNA against c-Myc. The in vitro invasion potentials of cells were evaluated by Transwell cell invasion assay. Results HBx induces HSP90alpha expression at the transcription level. The induction effect of HBx was inhibited after treatment with c-Myc inhibitor 10058-F4. In addition the luciferase activity of the HSP90alpha promoter analysis revealed that the HBx is directly involved in the c-Myc-mediated transcriptional activation of HSP90alpha. Furthermore HBx induces c-Myc expression by activation of Ras Raf ERK1 2 cascades which in turn results in activation of the c-Myc-mediated HSP90alpha promoter .

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