Upregulated expression of kappa light chain by Epstein-Barr virus encoded latent membrane protein 1 in nasopharyngeal carcinoma cells via NF-kappaB and AP-1 pathways.
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.
Liu
Hai-dan
HD
Cancer Research Institute, Xiangya School of Medicine, Central South University, Xiangya Road #110, Changsha, Hunan 410078, PR China.
Zheng
Hui
H
Li
Ming
M
Hu
Duo-sha
DS
Tang
Min
M
Cao
Ya
Y
D045744:Cell Line, Tumor; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000378:metabolism*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; D010446:Peptide Fragments; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; C439528:TAM67 peptide; D018808:Transcription Factor AP-1; D014763:Viral Matrix Proteins