| Autor: |
Pham LV; Department of Hematopathology, Box 54, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA., Tamayo AT, Yoshimura LC, Lin-Lee YC, Ford RJ |
| Jazyk: |
angličtina |
| Zdroj: |
Blood [Blood] 2005 Dec 01; Vol. 106 (12), pp. 3940-7. Date of Electronic Publication: 2005 Aug 11. |
| DOI: |
10.1182/blood-2005-03-1167 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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