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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 31, 2012 |
| Title |
NF-kB2 mutation targets survival, proliferation and differentiation pathways in the pathogenesis of B-lineage lymphomas |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Abnormal NF-kB2 activation has been reported in several types of human leukemia and lymphomas although the exact mechanisms and affected pathways are not clear. We have investigated these questions through the use of a unique transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma associated NF-kB2 mutant. Microarray analysis, verified at the RNA and protein level identified new downstream targets and confirmed established regulatory networks. 201 genes were significantly changed, with 126 being upregulated and 75 downregulated. Pathway analysis uncovered both known and unknown interactions between factors important in the development of human B cell lymphomas and multiple myeloma, including cyclins D1 and D2, TRAF1, CD27, BIRC5/survivin, IL-15 and IL-10. Critical roles for STAT3 and TNF receptors are highlighted. Six target genes of STAT3 were identified: cyclins D1and D2, IL-10, survivin, IL-21 and Blimp1. Interfering with STAT3 signaling induced apoptosis in multiple myeloma cell lines. Novel pathways for NF-kB2 are proposed that involve IL-10 and other genes in the differentiation of plasma cells, evasion of apoptosis and proliferation. These pathways were verified with publically available human microarrays. Several treatment strategies based on these findings are discussed.
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| Overall design |
RNA was isolated from the B cells of p80HT transgenic mice on the C57BL/6J x SJL/J background , which produced serum monoclonal immunoglobulin (M-protein) (n=3), and the B cells from wild type (WT) littermates (n=3) using Trizol reagent according to the manufacturer’s instructions (Invitrogen, Carlsbad, CA). RNA was further prepared with the Ambion WT Expression kit (Life Techologies Corp., Carlsbad, CA) then run on the Mouse Gene 1.0ST microarray chip (Affymetrix, Santa Clara, CA).
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| Contributor(s) |
McCarthy BA, Ding HF |
| Citation(s) |
22642622 |
| Submission date |
Jun 18, 2011 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Brian A McCarthy |
| E-mail(s) |
bmcc333@gmail.com
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| Phone |
347-256-3876
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| Organization name |
Georgia Health Sciences University
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| Department |
Cancer Center
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| Lab |
HF Ding
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| Street address |
1410 Laney Walker Blvd.
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| City |
Augusta |
| State/province |
GA |
| ZIP/Postal code |
30912 |
| Country |
USA |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA143995 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE30080_RAW.tar |
26.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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