A role of both NF-kappaB pathways in expression and transcription regulation of BAFF-R gene in multiple myeloma cells.

摘要

B-lymphocyte stimulator (BAFF) is a recently recognized member of the tumor necrosis factor ligand family (TNF) and a potent cell-survival factor expressed in many hematopoietic cells. BAFF regulates B-cell survival, differentiation, and proliferation by binding to three TNF receptors: TACI, BCMA, and BAFF-R. The mechanism involved in BAFF-R gene expression and regulation remains elusive. In this study, we examined BAFF-R gene expression, function, and regulation in multiple myeloma (KM3) cells. It was found that BAFF-BAFF-R induced cell survival by activating NF-kappaB1 pathway and NF-kappaB2 pathway. It was also found that NF-kappaB was an important transcription factor involved in regulating BAFF-R expression through one NF-kappaB binding site in the BAFF-R promoter, suggesting that inhibiting NF-kappaB could decrease the expression of BAFF-R mRNA and protein, and promote activity of BAFF-R gene. Our findings indicate that both NF-kappaB pathways are involved in the regulation of BAFF-R gene and the NF-kappaB-binding site of BAFF-R may be a new therapeutic target in this disease.