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Gene set: RAS_STROMA_DOWN_CROONQUIST (C2:PERT:0068)
Standard nameRAS_STROMA_DOWN_CROONQUIST
Systematic nameC2:PERT:0068
Brief descriptionGenes downregulated in multiple myeloma cells with N-ras-activating mutations versus those co-cultured with bone marrow stromal cells.
CategoryC2: Curated
Sub-categoryPERT: Experimental pertuberation
Full description or Abstract

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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. 
Publication URL12791645
External linksna
Keywords & MeSH headingsCell Communication/physiology,Coculture Techniques,Neoplastic/drug effects/physiology,Non-P.H.S.,Gene Expression Profiling,P.H.S.,Comparative Study,pharmacology,Phenotype,Multiple Myeloma,Humans,Tumor Cells,ras Proteins/metabolism,Stromal Cells,ras,Genes,genetics,Gene Expression Regulation,cytology,physiology,Cell Division/drug effects,Interleukin-6,Mitogen-Activated Protein Kinases/metabolism,Cultured/cytology
OrganismHuman
Contributed byKate Stafford
Source platformSeq_Accession
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Genes

21 genes, 24 accessions (Toggle view)

AccessionGeneTitleLinks
M33680CD81CD81 antigen (target of antiproliferative antibody 1)Source|GeneCards
X68277DUSP1dual specificity phosphatase 1Source|GeneCards
J03040SPARCsecreted protein, acidic, cysteine-rich (osteonectin)Source|GeneCards
M12125TPM2tropomyosin 2 (beta)Source|GeneCards
X75918NR4A2nuclear receptor subfamily 4, group A, member 2Source|GeneCards
M58459RPS4Y1ribosomal protein S4, Y-linked 1Source|GeneCards
K00650
M19267TPM1tropomyosin 1 (alpha)Source|GeneCards
V01512FOSv-fos FBJ murine osteosarcoma viral oncogene homologSource|GeneCards
AB029000SULF1sulfatase 1Source|GeneCards
AI557295
X04430IL6interleukin 6 (interferon, beta 2)Source|GeneCards
L19182IGFBP7insulin-like growth factor binding protein 7Source|GeneCards
J03464COL1A2collagen, type I, alpha 2Source|GeneCards
X13839ACTA2actin, alpha 2, smooth muscle, aortaSource|GeneCards
X78947CTGFconnective tissue growth factorSource|GeneCards
X52947GJA1gap junction protein, alpha 1, 43kDa (connexin 43)Source|GeneCards
S77154NR4A2nuclear receptor subfamily 4, group A, member 2Source|GeneCards
M35878IGFBP3insulin-like growth factor binding protein 3Source|GeneCards
M77349TGFBItransforming growth factor, beta-induced, 68kDaSource|GeneCards
D13666POSTNperiostin, osteoblast specific factorSource|GeneCards
M17733TMSB4Xthymosin, beta 4, X-linkedSource|GeneCards
X52022COL6A3collagen, type VI, alpha 3Source|GeneCards
U03057FSCN1fascin homolog 1, actin-bundling protein (Strongylocentrotus purpuratus)Source|GeneCards


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