[Gene expression profile in response to hepatitis B virus X gene by using an adenoviral vector].

Heui Yun Joo, Kwang Hyub Han, Wang Shick Ryu
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Abstract

Background/aims: Hepatitis B virus (HBV) is the etiological factor for hepatocellular carcinoma (HCC). Numerous evidence has indicated a link between chronic infection with HBV and the development of HCC. Among the four proteins encoded by HBV, Hepatitis B virus X gene(HBx), best characterized as a transcriptional transactivator, gained attention owing to its presumptive role in oncogenesis. Further, HBx has been shown to stimulate signal transduction pathways such as Ras-MAPK pathway, NF-kappa B, and Src kinase. The pleiotropic events caused by HBx may be the key to understanding the HBV-mediated oncogenicity. However, the specific roles of HBx in oncogenesis remain largely elusive. To explore the role of HBx in hepatocarcinogenesis, we examined the deregulation of host genes induced by HBx expression.

Methods: HBx was ectopically expressed in HepG2 cells using a recombinant adenovirus to transiently express HBx. Gene expression profiling of HBx was conducted on cDNA microarrays that contained 1,028 cDNAs.

Results: A number of oncogenes and genes that are involved in cell growth, DNA repair, cell cycle regulation, and cell motility were deregulated by HBx.

Conclusions: Theses results suggest that HBx regulates transcription in a way that contributes to the proliferation of hepatocytes, a probable early event of HCC.

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[利用腺病毒载体对乙型肝炎病毒X基因反应的基因表达谱]。
背景/目的:乙型肝炎病毒(HBV)是肝细胞癌(HCC)的病因。大量证据表明慢性HBV感染与HCC的发展之间存在联系。在HBV编码的四种蛋白中,乙型肝炎病毒X基因(HBx)被认为是一种转录反激活因子,因其在肿瘤发生中的作用而受到关注。此外,HBx已被证明可以刺激Ras-MAPK通路、NF-kappa B和Src激酶等信号转导通路。乙肝病毒引起的多效性事件可能是了解乙肝病毒介导的致癌性的关键。然而,HBx在肿瘤发生中的具体作用在很大程度上仍然难以捉摸。为了探讨HBx在肝癌发生中的作用,我们检测了HBx表达诱导的宿主基因的失调。方法:利用重组腺病毒在HepG2细胞中瞬时表达HBx。在包含1028个cDNA的cDNA微阵列上进行HBx基因表达谱分析。结果:许多致癌基因和参与细胞生长、DNA修复、细胞周期调控和细胞运动的基因被HBx解除调控。结论:这些结果表明,HBx以一种促进肝细胞增殖的方式调节转录,这可能是HCC的早期事件。
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