title: Binding of B-cell maturation antigen to B-cell activating factor induces survival of multiple myeloma cells by activating Akt and JNK signaling pathways.
abstract: B-cell maturation antigen (BCMA) is expressed on normal and malignant plasma cells and represents a potential target for therapeutic intervention. In this study, we characterized the mechanism underlying the protein kinase B (Akt) and c-Jun N-terminal kinase (JNK) pathways and BCMA interactions in regulating multiple myeloma (MM) cell survival. It was found that the expression levels of B cell-activating factor (BAFF) and BCMA were increased in MM cells as compared with those in normal controls. The proliferation of U266 cells was induced by recombinant human BAFF (rhBAFF) and could also be decreased by BCMA siRNA. The expression of Bcl-2 protein was up-regulated, and Bax protein was down-regulated after rhBAFF treatment, which could be reversed by BCMA siRNA. Similarly, the protein p-JNK and p-Akt were activated by rhBAFF and could be changed by BCMA siRNA. In addition, the BCMA mRNA and protein expression levels were decreased after treatment with Akt and JNK pathway inhibitors. These results suggest that Akt and JNK pathways are involved in the regulation of BCMA. A novel BAFF/BCMA signalling pathway in MM may be a new therapeutic target for MM.
authors.affiliation: Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Xianjuan
authors.initials: X
authors.lastname: Shen
authors.affiliation: Nantong University, Nantong, China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Qi
authors.affiliation: Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Wu
authors.affiliation: Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, China.|Nantong University, Nantong, China.|Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Ju
mesh_terms: D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor / Q000378:metabolism*; D053301:B-Cell Maturation Antigen / Q000378:metabolism*; D001665:Binding Sites; D002470:Cell Survival; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology*; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Akt signalling pathway; B cell-activating factor (BAFF); B-cell maturation antigen (BCMA); JNK signalling pathway; multiple myeloma (MM)