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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
16
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pubmed:dateCreated |
1995-9-7
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pubmed:abstractText |
Multiple myeloma (MM) is a late-stage B-cell cancer with an unknown etiology. Activating mutations of the N-ras and K-ras oncogenes occur with a high frequency in myeloma and, therefore, may play a role in the pathogenesis of the disease. To study the role of N-ras-activating mutations in the regulation of myeloma tumor growth, we introduced a constitutively active N-ras cDNA containing a glutamine to arginine (CAA-CGA) amino acid substitution at codon 61 into the interleukin 6 (IL-6)-dependent myeloma cell line ANBL6. Expression of the mutant N-ras cDNA resulted in significant IL-6-independent growth, as well as augmentation of growth at suboptimal concentrations of IL-6. The IL-6-independent growth pattern was not the result of activation of autocrine IL-6 production in the mutant N-ras-expressing population because neutralizing antibodies to the IL-6 receptor and to IL-6 had no effect on the rate of DNA synthesis in the absence of IL-6. Furthermore, mutant N-ras expression decreased the percentage of cells undergoing apoptosis in the absence of IL-6. These data suggest that activating mutations of the ras oncogenes may result in growth factor independence accompanied by a suppression of apoptosis in MM. Therefore, the use of therapies designed to block IL-6 action in MM may have less of an impact on tumors bearing activated ras mutations.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Aug
|
pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
15
|
pubmed:volume |
55
|
pubmed:geneSymbol |
N-ras
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
3640-6
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:7627974-Apoptosis,
pubmed-meshheading:7627974-Base Sequence,
pubmed-meshheading:7627974-Cell Division,
pubmed-meshheading:7627974-Cell Survival,
pubmed-meshheading:7627974-DNA Primers,
pubmed-meshheading:7627974-Genes, ras,
pubmed-meshheading:7627974-Growth Substances,
pubmed-meshheading:7627974-Interleukin-6,
pubmed-meshheading:7627974-Molecular Sequence Data,
pubmed-meshheading:7627974-Multiple Myeloma,
pubmed-meshheading:7627974-Point Mutation,
pubmed-meshheading:7627974-Proto-Oncogene Proteins p21(ras),
pubmed-meshheading:7627974-Transfection,
pubmed-meshheading:7627974-Tumor Cells, Cultured
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pubmed:year |
1995
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pubmed:articleTitle |
Introduction of an activated N-ras oncogene alters the growth characteristics of the interleukin 6-dependent myeloma cell line ANBL6.
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pubmed:affiliation |
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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