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

我们已经证明了诱发鼻咽癌的EB病毒-LMP1通过Siah1在鼻咽上皮细胞中稳定hTF1α。然而，LMP1下调了Burkitt淋巴瘤细胞系中Siah1的表达。在这项研究中，我们研究了Siah1在各种EBV相关肿瘤中的功能。免疫组织化学方法检测LMP1、HIF1α和SiHA1的表达。最后，我们发现Siah1与LMP1在鼻咽癌中的表达密切相关。然而，在其他EBV相关肿瘤中没有相关性。由于我们假设不仅LMP1诱导刺激而且低氧条件本身也影响鼻咽癌组织中HIF1-α的表达，所以我们研究了LMP1表达的鼻咽癌细胞株在低氧刺激和不低氧刺激下的表达。低氧条件和LMP1表达的协同作用在体外和体内通过免疫缺陷小鼠增加了它们的HIF1α的表达。缺氧与LMP1表达的相关性可能是了解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.