Molecular biological analysis of Siah1 in EBV related tumor including nasopharyngeal cancer

我们已经证明，诱导鼻咽癌（NPC）的EBV-LMP 1通过Siah 1稳定鼻咽上皮细胞中的HTF 1 α。然而，LMP 1下调伯基特淋巴瘤细胞系中的Siah 1。在这项研究中，我们检查了Siah 1在各种EB病毒相关肿瘤中的功能。我们通过免疫组化检测LMP 1、HIF 1 α和Siah 1的表达。结果发现Siah 1与LMP 1在鼻咽癌中的表达呈强相关。然而，在其他EBV相关肿瘤中没有相关性。由于我们假设HIF 1-α的表达不仅受LMP 1诱导的刺激影响，而且缺氧条件本身也会影响HIF 1-α的表达，因此我们用低氧箱研究了LMP 1表达的鼻咽癌细胞系在缺氧刺激和无缺氧刺激下的表达。缺氧条件和LMP 1表达的协同作用增加了它们在体外和体内使用免疫缺陷小鼠的HIF 1 α表达。缺氧与LMP 1表达的相互影响可能是理解EBV相关肿瘤的关键。

We have shown that EBV-LMP1 that induced nasopharyngeal cancer (NPC), stabilizes HTF1α via Siah1in nasopharyngeal epithelial cells. However LMP1 downregulates Siah1 in Burkitt lymphoma cell lines. In this study, we examined Siah1 function in various EBV-related tumors. We investigated expression of LMP1, HIF1α, and Siah1 by immunohistochemistry. Finally we found that the expression of Siah1 was correlated with LMP1 strongly in NPC. However there was no correlation in other EBV-related tumors. Since we hypothesize not only LMP1 inducible stimulation but hypoxia condition itself also affects HIF1-α expressions in NPC tissues, we investigated with LMP1 expressed nasopharyngeal cell lines with or without hypoxia stimulation with hypoxia chamber. Synergistic effect of hypoxic conditions and LMP1 expression increased their HIF1α expression in vitro and in vivo using immunodeficinet mice. The crosstalk of hypoxia and LMP1 expression may be a key of understanding EBV-related tumors.