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

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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.