Liu Hai-dan, Zheng Hui, Li Ming, Hu Duo-sha, Tang Min, Cao Ya
Cancer Research Institute, Xiangya School of Medicine, Central South University, Xiangya Road #110, Changsha, Hunan 410078, PR China.
Cell Signal. 2007 Feb;19(2):419-27. doi: 10.1016/j.cellsig.2006.07.012. Epub 2006 Sep 18.
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 Bay11-7082 and SP600125, inhibitors of JNK and NF-kappaB, respectively, inhibited LMP1-augmented kappa light chain expression in NPC cells. LMP1-positive NPC cells expressing the dominant-negative mutant of IkappaBalpha (DNMIkappaBalpha) 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-kappaB and AP-1 signaling pathways. The present study provided some hints of possible mechanisms by which human cancer cells of epithelial origin produced immunoglobulins.
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，包括鼻咽癌细胞系，能够表达免疫球蛋白。此外，我们之前发现EB病毒编码的潜伏膜蛋白1（LMP1）可上调鼻咽癌细胞中κ轻链的表达。在此，通过蛋白质免疫印迹法及细胞内κ染色的流式细胞术分析表明，使用靶向LMP1的脱氧核酶可抑制κ表达的上调，并且分别作为JNK和NF-κB抑制剂的Bay11-7082和SP600125可抑制LMP1增强的鼻咽癌细胞中κ轻链的表达。与亲代细胞相比，表达IκBα显性负性突变体（DNMIκBα）或c-Jun（TAM67）的LMP1阳性鼻咽癌细胞产生的κ明显减少。这些结果表明，LMP1通过激活NF-κB和AP-1信号通路提高κ轻链水平。本研究为上皮来源的人类癌细胞产生免疫球蛋白的可能机制提供了一些线索。
