Gene Set: CROONQUIST_NRAS_SIGNALING_DN

Standard name CROONQUIST_NRAS_SIGNALING_DN
Systematic name M10739
Brief description Genes down-regulated in ANBL-6 cell line (multiple myeloma, MM) expressing a constantly active form of NRAS [GeneID=4893] off a plasmid vector compared to those grown in the presence of IL6 [GeneID=3569].
Full description or abstract ANBL-6, a myeloma cell line, proliferates in response to interleukin 6 (IL-6) stimulation, coculture with bone marrow stromal cells, and when harboring a constitutively active mutant N-ras gene. Eighteen samples, including 4 IL-6-treated, 3 mutant N-ras-transfected, 3 normal stroma-stimulated, 2 multiple myeloma (MM) stroma-stimulated, and 6 untreated controls were profiled using microarrays interrogating 12 626 genes. Global hierarchical clustering analysis distinguished at least 6 unique expression signatures. Notably, the different stimuli altered distinct functional gene programs. Class comparison analysis (P =.001) revealed 138 genes (54% involved in cell cycle) that distinguished IL-6-stimulated versus nontreated samples. Eighty-seven genes distinguished stroma-stimulated versus IL-6-treated samples (22% encoded for extracellular matrix [ECM] proteins). A total of 130 genes distinguished N-ras transfectants versus IL-6-treated samples (26% involved in metabolism). A total of 157 genes, 20% of these involved in signaling, distinguished N-ras from stroma-interacting samples. All 3 stimuli shared 347 genes, mostly of metabolic function. Genes that distinguished MM1 from MM4 clinical groups were induced at least by one treatment. Notably, only 3 genes (ETV5, DUSP6, and KIAA0735) are uniquely induced in mutant ras-containing cells. We have demonstrated gene expression patterns in myeloma cells that distinguish an intrinsic genetic transformation event and patterns derived from both soluble factors and cell contacts in the bone marrow microenvironment.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 12791645   Authors: Croonquist PA,Linden MA,Zhao F,Van Ness BG
Exact source Suppl. Data 2C: Table 2S: Fold-diff in geom means < 1
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform HUMAN_SEQ_ACCESSION
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