Upregulated expression of kappa light chain by Epstein-Barr virus encoded latent membrane protein 1 in nasopharyngeal carcinoma cells via NF-κB and AP-1 pathways

Upregulated expression of kappa light chain by Epstein-Barr virus encoded latent membrane protein 1 in nasopharyngeal carcinoma cells via NF-κB and AP-1 pathways
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DOI:
10.1016/j.cellsig.2006.07.012
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发表时间:
2007-02-01
影响因子:
4.8
通讯作者:
Cao, Ya
Cao, Ya
中科院分区:
生物学2区
文献类型:
--
作者:
Liu, Hai-dan;Zheng, Hui;Cao, Ya

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B淋巴细胞通常被认为是免疫球蛋白的唯一来源。然而,越来越多的证据表明,一些人类上皮癌细胞系,包括鼻咽癌(NPC)细胞系,表达免疫球蛋白。此外,我们之前发现鼻咽癌细胞中κ轻链的表达可以被EBV编码的潜伏膜蛋白1(LMP1)上调。此处,细胞内 kappa 染色的蛋白质印迹和流式细胞术分析表明,使用 LMP1 靶向 DNAzyme 抑制了 kappa 表达的上调,并且 Bay 11-7082 和 SP600125(分别是 JNK 和 NF-kappa B 的抑制剂)抑制了 NPC 细胞中 LMP1 增强的 kappa 轻链表达。表达 I kappa B α (DNMI kappa B α) 或 c-Jun (TAM67) 显性失活突变体的 LMP1 阳性 NPC 细胞与其亲代细胞相比,表现出 kappa 产生显着降低。这些结果表明 LMP1 通过激活 NF-kappa B 和 AP-1 信号通路来升高 kappa 轻链。本研究提供了一些关于上皮来源的人类癌细胞产生免疫球蛋白的可能机制的线索。 (c) 2006 Elsevier Inc. 保留所有权利。
B lymphocytes are generally considered to be the only source of immunoglobulins. However, increasing evidence revealed that some human epithelial cancer cell lines, including nasopharyngeal carcinoma (NPC) cell lines, expressed immunoglobulins. Moreover, we previously found that expression of kappa light chain in NPC cells could be upregulated by EBV-encoded latent membrane protein 1 (LMP1). Here, Western blot and flow cytometric analysis of intracellular kappa staining indicated that upregulation of the expression of kappa was inhibited by using LMP1-targeted DNAzyme and that Bay 11-7082 and SP600125, inhibitors of JNK and NF-kappa B, respectively, inhibited LMP1-augmented kappa light chain expression in NPC cells. LMP1-positive NPC cells expressing the dominant-negative mutant of I kappa B alpha (DNMI kappa B alpha) or of c-Jun (TAM67) exhibited significantly decreasing kappa production compared with their parental cells. These results suggest that LMP1 elevated kappa light chain through activation of the NF-kappa B and AP-1 signaling pathways. The present study provided some hints of possible mechanisms by which human cancer cells of epithelial origin produced immunoglobulins. (c) 2006 Elsevier Inc. All rights reserved.