Epstein-Barr virus protein can upregulate cyclo-oxygenase-2 expression through association with the suppressor of metastasis Nm23-H1
Epstein-Barr virus protein can upregulate cyclo-oxygenase-2 expression through association with the suppressor of metastasis Nm23-H1
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DOI：
10.1128/jvi.80.3.1321-1331.2006
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发表时间：
2006-02-01
影响因子：
5.4
通讯作者：
Robertson, ES
中科院分区：
文献类型：
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作者：
Kaul, R;Verma, SC;Robertson, ES
以前的研究已经证明了EB病毒(EBV)核抗原3C(EBNA3C)与转移抑制基因Nm23-H1之间的相互作用(C.Subramanian，M.A.Cotter 11和E.S.Robertson，NAT)。地中海医院。2001年7：350-355)。EBNA3C在体外可逆转Nm23-H1抑制Burkitt淋巴瘤和乳腺癌细胞系迁移的能力。EBNA3C通过调节一些细胞和病毒启动子的转录，以及靶向和改变转移抑制基因Nm23-H1的转录活性，在EBV相关的人类癌症中发挥作用。环氧合酶-2(COX-2)是一种在炎症中起重要作用的诱导性酶，在多种癌症中过表达，并可影响细胞迁移。在这份报告中，我们发现Nm23-H1和EBNA3C可以在EBV感染和转化的背景下调节COX-2的表达。EBV阳性细胞的COX-2水平始终高于EBV阴性细胞。此外，我们还表明，在荧光素酶报告分析中，Nm23-H1可以上调COX-2启动子元件，而EBNA3C本身并不影响反应水平，但当与Nm23-H1共表达时，明显促进了加性增加。COX-2表达的下游效应也被评估，显示前列腺素E_1水平随着Nm23-H1的增加而增加，并且在EBNA3C的存在下存在一定程度的协同作用。这种反应主要是通过环状AMP反应元件和核因子-kappaB位点来实现的。这些研究表明，COX-2在EBV相关的人类癌症中可能起到作用。
Previous studies have demonstrated the interaction between the Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) and the metastatic suppressor Nm23-H1 both in vitro and in vivo (C. Subramanian, M. A. Cotter 11, and E. S. Robertson, Nat. Med. 7:350-355, 2001). EBNA3C can reverse the ability of Nm23-H1 to suppress migration of Burkitt's lymphoma and breast carcinoma cell lines in vitro. EBNA3C contributes to EBV-associated human cancers by regulating transcription of a number of cellular and viral promoters and by targeting and altering the transcription activities of the metastasis suppressor Nm23-H1. Cyclo-oxygenase-2 (COX-2), an inducible enzyme important in inflammation, is overexpressed in a variety of cancers and can influence cell migration. In this report we show that Nm23-H1 and EBNA3C can modulate expression of COX-2 in the context of EBV infection and transformation. The levels of COX-2 were consistently higher in EBV-positive cells than in EBV-negative cells. Additionally, we show that Nm23-H1 can upregulate the COX-2 promoter element in luciferase reporter assays, whereas EBNA3C alone did not affect the level of response but clearly contributed to an additive increase when coexpressed with Nm23-H1. The downstream effect of COX-2 expression was also evaluated and showed that prostaglandin E, levels increased with Nm23-H1 and that there was some level of cooperativity in the presence of EBNA3C. The majority of this response was mediated through the cyclic AMP response element and NF-kappa B sites. These studies suggest a potential role for COX-2 in EBV-associated human cancers.