PMID- 16497967
OWN - NLM
STAT- MEDLINE
DCOM- 20060629
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 107
IP  - 11
DP  - 2006 Jun 1
TI  - Constitutive NF-kappaB and NFAT activation leads to stimulation of the BLyS 
      survival pathway in aggressive B-cell lymphomas.
PG  - 4540-8
AB  - B-lymphocyte stimulator (BLyS), a relatively recently recognized member of the 
      tumor necrosis factor ligand family (TNF), is a potent cell-survival factor 
      expressed in many hematopoietic cells. BLyS binds to 3 TNF-R receptors, TACI, 
      BCMA, BAFF-R, to regulate B-cell survival, differentiation, and proliferation. 
      The mechanisms involved in BLYS gene expression and regulation are still 
      incompletely understood. In this study, we examined BLYS gene expression, 
      function, and regulation in B-cell non-Hodgkin lymphoma (NHL-B) cells. Our 
      studies indicate that BLyS is constitutively expressed in aggressive NHL-B cells, 
      including large B-cell lymphoma (LBCL) and mantle cell lymphoma (MCL), playing an 
      important role in the survival and proliferation of malignant B cells. We found 
      that 2 important transcription factors, NF-kappaB and NFAT, are involved in 
      regulating BLyS expression through at least one NF-kappaB and 2 NFAT binding 
      sites in the BLYS promoter. We also provide evidence suggesting that the 
      constitutive activation of NF-kappaB and BLyS in NHL-B cells forms a positive 
      feedback loop associated with lymphoma cell survival and proliferation. Our 
      findings indicate that constitutive NF-kappaB and NFAT activations are crucial 
      transcriptional regulators of the BLyS survival pathway in malignant B cells that 
      could be therapeutic targets in aggressive NHL-B.
FAU - Fu, Lingchen
AU  - Fu L
AD  - Department of Hematopathology, University of Texas M. D. Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Lin-Lee, Yen-Chiu
AU  - Lin-Lee YC
FAU - Pham, Lan V
AU  - Pham LV
FAU - Tamayo, Archito
AU  - Tamayo A
FAU - Yoshimura, Linda
AU  - Yoshimura L
FAU - Ford, Richard J
AU  - Ford RJ
LA  - eng
GR  - CA-16672-26/CA/NCI NIH HHS/United States
GR  - CA-R01-100836/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060223
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (B-Cell Activating Factor)
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (TNFSF13B protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Apoptosis Regulatory Proteins
MH  - B-Cell Activating Factor
MH  - Binding Sites
MH  - Cell Survival
MH  - Feedback, Physiological
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Lymphoma, B-Cell/metabolism/*pathology
MH  - Membrane Proteins/genetics/*metabolism
MH  - NF-kappa B/*metabolism/physiology
MH  - NFATC Transcription Factors/*metabolism/physiology
MH  - Promoter Regions, Genetic
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
PMC - PMC1895801
EDAT- 2006/02/25 09:00
MHDA- 2006/06/30 09:00
PMCR- 2007/06/01
CRDT- 2006/02/25 09:00
PHST- 2006/02/25 09:00 [pubmed]
PHST- 2006/06/30 09:00 [medline]
PHST- 2006/02/25 09:00 [entrez]
PHST- 2007/06/01 00:00 [pmc-release]
AID - S0006-4971(20)64593-1 [pii]
AID - 4540 [pii]
AID - 10.1182/blood-2005-10-4042 [doi]
PST - ppublish
SO  - Blood. 2006 Jun 1;107(11):4540-8. doi: 10.1182/blood-2005-10-4042. Epub 2006 Feb 
      23.