PMID- 16099873
OWN - NLM
STAT- MEDLINE
DCOM- 20060118
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 106
IP  - 12
DP  - 2005 Dec 1
TI  - Constitutive NF-kappaB and NFAT activation in aggressive B-cell lymphomas 
      synergistically activates the CD154 gene and maintains lymphoma cell survival.
PG  - 3940-7
AB  - Abnormalities in B-lymphocyte CD40 ligand (CD154) expression have been described 
      for a number of immunologic diseases, including B-cell lymphomas. Although 
      functional analysis of the CD154 gene and protein has been extensive, little is 
      known about the mechanisms controlling CD154 expression in activated T cells, and 
      even less is known for normal and malignant B cells. In this study we describe 
      the transcriptional mechanism controlling CD154 expression in large B-cell 
      lymphoma (LBCL). We show that the nuclear factor of activated T cells (NFAT) 
      transcription factor is also constitutively activated in LBCL. We demonstrate 
      that the constitutively active NFATc1 and c-rel members of the NFAT and nuclear 
      factor-kappaB (NF-kappaB) families of transcription factors, respectively, 
      directly interact with each other, bind to the CD154 promoter, and 
      synergistically activate CD154 gene transcription. Down-regulation of NFATc1 or 
      c-rel with small interfering RNA (siRNA) or chemical inhibitors inhibits CD154 
      gene transcription and lymphoma cell growth. These findings suggest that 
      targeting NF-kappaB and NFAT, by inhibiting the expression of these transcription 
      factors, or interdicting their interaction may provide a therapeutic rationale 
      for patients with non-Hodgkin lymphoma of B-cell origin, and possibly other 
      disorders that display dysregulated CD154 expression.
FAU - Pham, Lan V
AU  - Pham LV
AD  - Department of Hematopathology, Box 54, The University of Texas M. D. Anderson 
      Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
FAU - Tamayo, Archito T
AU  - Tamayo AT
FAU - Yoshimura, Linda C
AU  - Yoshimura LC
FAU - Lin-Lee, Yen-Chiu
AU  - Lin-Lee YC
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 - 20050811
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (NF-kappa B)
RN  - 0 (NFATC Transcription Factors)
RN  - 147205-72-9 (CD40 Ligand)
SB  - IM
MH  - CD40 Ligand/*genetics
MH  - Cell Line, Tumor
MH  - Cell Survival/physiology
MH  - Electrophoretic Mobility Shift Assay
MH  - Enzyme Activation/physiology
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunoprecipitation
MH  - In Situ Nick-End Labeling
MH  - Lymphoma, B-Cell/*genetics
MH  - Lymphoma, Large B-Cell, Diffuse/*genetics
MH  - Microscopy, Confocal
MH  - NF-kappa B/*metabolism
MH  - NFATC Transcription Factors/*metabolism
MH  - Transcriptional Activation
MH  - Transfection
PMC - PMC1895110
EDAT- 2005/08/16 09:00
MHDA- 2006/01/19 09:00
PMCR- 2006/12/01
CRDT- 2005/08/16 09:00
PHST- 2005/08/16 09:00 [pubmed]
PHST- 2006/01/19 09:00 [medline]
PHST- 2005/08/16 09:00 [entrez]
PHST- 2006/12/01 00:00 [pmc-release]
AID - S0006-4971(20)66933-6 [pii]
AID - 3940 [pii]
AID - 10.1182/blood-2005-03-1167 [doi]
PST - ppublish
SO  - Blood. 2005 Dec 1;106(12):3940-7. doi: 10.1182/blood-2005-03-1167. Epub 2005 Aug 
      11.