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Prepublished online as a Blood First Edition Paper on June 5, 2003; DOI 10.1182/blood-2003-04-1227. This Article Full Text (PDF) Supplemental Data Sets All Versions of this Article: 2003-04-1227v1 102/7/2581    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Croonquist, P. A Articles by Van Ness, B. G Search for Related Content PubMed PubMed Citation Articles by Croonquist, P. A Articles by Van Ness, B. G Social Bookmarking                   What's this? Submitted April 18, 2003 Accepted May 27, 2003 Gene profiling of a myeloma cell line reveals similarities and unique signatures among IL-6 response, N-ras activating mutations and co-culture with bone marrow stromal cells Paula A Croonquist, Michael A Linden, Fangyi Zhao, and Brian G Van Ness* The Graduate Program in Molecular, Cellular, Developmental Biology, and Genetics, University of Minnesota, Minneapolis, MN, USA The Graduate Program in Microbiology, Immunology and Cancer Biology, University of Minnesota, Minneapolis, MN, USA; Medical School, University of Minnesota, Minneapolis, MN, USA The Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN, USA; The Cancer Center, University of Minnesota, Minneapolis, MN, USA * Corresponding author; email: vanne001{at}tc.umn.edu. ANBL-6, a myeloma cell line, proliferates in response to IL-6 stimulation, co-culture 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 MM stroma-stimulated and 6 untreated controls were profiled using microarrays interrogating 12,626 genes. Global hierarchical clustering analysis distinguished at least six unique expression signatures. Notably, the different stimuli altered distinct functional gene programs. Class comparison analysis (P= 0.001) revealed 138 genes (54% involved in cell cycle) that distinguished IL-6-stimulated versus non-treated samples. 87 genes distinguished stroma-stimulated versus IL-6-treated samples (22% encoded for ECM proteins). 130 genes distinguished N-ras transfectants versus IL-6-treated samples (26% involved in metabolism). 157 genes, 20% of these involved in signaling, distinguished N-ras from stroma-interacting samples. All three 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 three genes (ETV5, DUSP6 and KIAA0735) are uniquely induced in mutant N-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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: U.-M. Fagerli, R. U. Holt, T. Holien, T. K. Vaatsveen, F. Zhan, K. W. Egeberg, B. Barlogie, A. Waage, H. Aarset, H. Y. Dai, et al. Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells Blood, January 15, 2008; 111(2): 806 - 815. [Abstract] [Full Text] [PDF] K. Mahtouk, D. Hose, J. De Vos, J. Moreaux, M. Jourdan, J. F. Rossi, T. Reme, H. Goldschmidt, and B. Klein Input of DNA Microarrays to Identify Novel Mechanisms in Multiple Myeloma Biology and Therapeutic Applications Clin. Cancer Res., December 15, 2007; 13(24): 7289 - 7295. [Abstract] [Full Text] [PDF] K. L.M. Boylan, M. A. Gosse, S. E. Staggs, S. Janz, S. Grindle, G. S. Kansas, and B. G. Van Ness A Transgenic Mouse Model of Plasma Cell Malignancy Shows Phenotypic, Cytogenetic, and Gene Expression Heterogeneity Similar to Human Multiple Myeloma Cancer Res., May 1, 2007; 67(9): 4069 - 4078. [Abstract] [Full Text] [PDF] X.-Y. Pei, Y. Dai, and S. Grant Synergistic Induction of Oxidative Injury and Apoptosis in Human Multiple Myeloma Cells by the Proteasome Inhibitor Bortezomib and Histone Deacetylase Inhibitors Clin. Cancer Res., June 1, 2004; 10(11): 3839 - 3852. [Abstract] [Full Text] [PDF] K. Brocke-Heidrich, A. K. Kretzschmar, G. Pfeifer, C. Henze, D. Loffler, D. Koczan, H.-J. Thiesen, R. Burger, M. Gramatzki, and F. Horn Interleukin-6-dependent gene expression profiles in multiple myeloma INA-6 cells reveal a Bcl-2 family-independent survival pathway closely associated with Stat3 activation Blood, January 1, 2004; 103(1): 242 - 251. [Abstract] [Full Text] [PDF]

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