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EB 病毒潜伏膜蛋白 1 诱导转移性鼻咽癌中的 Snail 和上皮-间充质转化。

Epstein-Barr Virus latent membrane protein 1 induces Snail and epithelial-mesenchymal transition in metastatic nasopharyngeal carcinoma.

机构信息

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB# 7295, Chapel Hill, NC 27599-7295, USA.

出版信息

Br J Cancer. 2011 Mar 29;104(7):1160-7. doi: 10.1038/bjc.2011.38. Epub 2011 Mar 8.

DOI:10.1038/bjc.2011.38
PMID:21386845
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3068490/
Abstract

BACKGROUND

Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) is distinctive among head-and-neck cancers in its undifferentiated histopathology and highly metastatic character. We have recently investigated the involvement of epithelial-mesenchymal transition (EMT) in NPC. In a previous study, we found a close association of expression of LMP1, the principal EBV oncoprotein, with expression of Twist and induction of EMT.

METHODS

We analysed expression of Snail in 41 NPC tissues by immunohistochemistry. The role of Twist as well as Snail in EMT of NPC was investigated by using NP69SV40T human nasopharyngeal cells.

RESULTS

In NPC tissues, overexpression of Snail is associated with expression of LMP1 in carcinomatous cells. In addition, expression of Snail positively correlated with metastasis and independently correlated inversely with expression of E-cadherin. Expression of Twist had no association with expression of E-cadherin. Further, in a human nasopharyngeal cell line, LMP1 induces EMT and its associated cellular motility and invasiveness. Expression of Snail is induced by LMP1 in these cells, and small hairpin RNA (shRNA) to Snail reversed the cellular changes. By contrast, Twist did not produce EMT in these nasopharyngeal cells.

CONCLUSIONS

This study strengthens the association of EMT with the metastatic behaviour of NPC. These results suggest that induction of Snail by the EBV oncoprotein LMP1 has a pivotal role in EMT in NPC.

摘要

背景

EBV 相关的鼻咽癌（NPC）在其未分化的组织病理学和高度转移性特征方面与头颈部癌症不同。我们最近研究了 EMT 在上皮间充质转化（EMT）在 NPC 中的作用。在之前的研究中，我们发现 LMP1（主要 EBV 癌蛋白）的表达与 Twist 的表达和 EMT 的诱导密切相关。

方法

我们通过免疫组织化学分析了 41 例 NPC 组织中 Snail 的表达。我们使用 NP69SV40T 人鼻咽细胞研究了 Twist 以及 Snail 在 NPC 中的 EMT 作用。

结果

在 NPC 组织中，Snail 的过表达与癌性细胞中 LMP1 的表达相关。此外，Snail 的表达与转移呈正相关，并且与 E-钙粘蛋白的表达独立负相关。Twist 的表达与 E-钙粘蛋白的表达无关。此外，在人鼻咽细胞系中，LMP1 诱导 EMT 及其相关的细胞迁移和侵袭。LMP1 在这些细胞中诱导 Snail 的表达，并且针对 Snail 的短发夹 RNA（shRNA）逆转了细胞变化。相比之下，Twist 并没有在这些鼻咽细胞中产生 EMT。

结论

这项研究加强了 EMT 与 NPC 转移行为的关联。这些结果表明，EBV 癌蛋白 LMP1 诱导的 Snail 表达在 NPC 中的 EMT 中具有关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f4/3068490/a8bb67c2f28f/bjc201138f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f4/3068490/46a709dbfe4b/bjc201138f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f4/3068490/89a9d762f747/bjc201138f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f4/3068490/072dfb56331d/bjc201138f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f4/3068490/a8bb67c2f28f/bjc201138f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f4/3068490/46a709dbfe4b/bjc201138f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f4/3068490/89a9d762f747/bjc201138f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f4/3068490/072dfb56331d/bjc201138f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f4/3068490/a8bb67c2f28f/bjc201138f4.jpg

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