title: A role of both NF-κB pathways in expression and transcription regulation of BAFF-R gene in multiple myeloma cells.
abstract: 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-κB1 pathway and NF-κB2 pathway. It was also found that NF-κB was an important transcription factor involved in regulating BAFF-R expression through one NF-κB binding site in the BAFF-R promoter, suggesting that inhibiting NF-κB could decrease the expression of BAFF-R mRNA and protein, and promote activity of BAFF-R gene. Our findings indicate that both NF-κB pathways are involved in the regulation of BAFF-R gene and the NF-κB-binding site of BAFF-R may be a new therapeutic target in this disease.
authors: Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, People's Republic of China.
authors: Xianjuan
authors: X
authors: Shen
authors: Wencai
authors: W
authors: Zhu
authors: Xia
authors: X
authors: Zhang
authors: Guang
authors: G
authors: Xu
authors: Shaoqing
authors: S
authors: Ju
references: J Leukoc Biol. 1999 May;65(5):680-3
references: 10331498
references: Science. 2001 Aug 24;293(5534):1495-9
references: 11520989
references: Blood. 2009 May 7;113(19):4627-36
references: 19258594
references: Histopathology. 2009 Jan;54(2):221-32
references: 19207947
references: PLoS One. 2009;4(5):e5456
references: 19421318
references: J Biol Chem. 2002 May 10;277(19):16639-47
references: 11872748
references: Annu Rev Immunol. 2000;18:621-63
references: 10837071
references: Nat Immunol. 2002 Sep;3(9):822-9
references: 12154359
references: J Immunol. 2009 Sep 15;183(6):3561-7
references: 19726767
references: Blood. 2005 Jan 15;105(2):804-11
references: 15454494
references: Acta Biochim Biophys Sin (Shanghai). 2008 Jun;40(6):505-12
references: 18535749
references: Science. 2001 Sep 14;293(5537):2108-11
references: 11509692
references: Nature. 2000 Apr 27;404(6781):995-9
references: 10801128
references: J Immunol. 2007 Sep 15;179(6):3872-80
references: 17785824
references: Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3370-5
references: 10716715
references: Nat Immunol. 2001 Jul;2(7):632-7
references: 11429548
references: Biochemistry. 2005 Feb 15;44(6):1919-31
references: 15697217
references: Eur J Haematol. 2009 Apr;82(4):267-76
references: 19187273
references: Immunity. 2002 Oct;17(4):515-24
references: 12387744
references: Cancer Cell. 2004 Sep;6(3):203-8
references: 15380510
references: Blood. 2004 Oct 15;104(8):2247-53
references: 15251985
references: Blood. 2007 Jan 15;109(2):703-10
references: 16973958
references: Science. 1999 Jul 9;285(5425):260-3
references: 10398604
references: J Biol Chem. 2000 Mar 31;275(13):9377-84
references: 10734081
references: Clin Biochem. 2006 Dec;39(12):1131-7
references: 17069785
references: J Clin Invest. 2001 Feb;107(3):241-6
references: 11160144
references: Blood. 2004 Jan 15;103(2):679-88
references: 14504101
references: Annu Rev Immunol. 1998;16:225-60
references: 9597130
references: Blood. 2006 Jun 1;107(11):4540-8
references: 16497967
references: J Immunol. 2004 Jan 15;172(2):812-22
references: 14707051