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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
1995-12-28
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pubmed:abstractText |
Coexpression of the proto-oncogenes c-myc and bcl-2 under the control of the immunoglobulin enhancer E mu provokes the rapid development of primitive lymphoid tumors in transgenic mice. In the present study we show that the myc family members N-myc and L-myc also cooperate with bcl-2 in oncogenesis and can provoke the development of more mature pre-B, B and T cell type lymphomas. The analysis of prelymphomatous B-cells from single E mu N-myc and bcl-2-Ig transgenic animals and from young, tumor free, double transgenic E mu N-myc/bcl-2-Ig mice revealed that E mu directed expression of N-myc leads to very rapid apoptosis after explantation and culturing compared to B-cells from normal mice. As expected, B-cells from bcl-2-Ig transgenics were protected to a certain degree from apoptosis. Strikingly however, B-cells from E mu N-myc/bcl-2-Ig double transgenic animals were found to be almost completely resistant towards a number of different apoptotic stimuli. Furthermore, after treatment with H2O2, which can trigger apoptosis, B-cells from E mu N-myc animals reach levels of intracellular free Ca2+ concentrations that are comparable to B-cells from normal mice, whereas B-cells from bcl-2-Ig or E mu N-myc/bcl-2-Ig double transgenic mice show no increase in intracellular Ca2+ concentrations after stimulation with H2O2. These findings suggest that the prevention of apoptosis conferred by bcl-2 correlates with the inhibition of intracellular Ca2+ fluxes whereas induction of apoptosis mediated by N-myc requires normal Ca2+ levels. We hypothesize therefore that the regulation of intracellular Ca2+ concentrations represent one important parameter in the oncogenic cooperation between bcl-2 and N-myc.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0950-9232
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2165-74
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:7478538-Animals,
pubmed-meshheading:7478538-Apoptosis,
pubmed-meshheading:7478538-B-Lymphocytes,
pubmed-meshheading:7478538-Calcium,
pubmed-meshheading:7478538-Cell Differentiation,
pubmed-meshheading:7478538-Cell Survival,
pubmed-meshheading:7478538-Female,
pubmed-meshheading:7478538-Gene Expression,
pubmed-meshheading:7478538-Genes, myc,
pubmed-meshheading:7478538-Hydrogen Peroxide,
pubmed-meshheading:7478538-Intracellular Fluid,
pubmed-meshheading:7478538-Lymphoma, B-Cell,
pubmed-meshheading:7478538-Male,
pubmed-meshheading:7478538-Mice,
pubmed-meshheading:7478538-Mice, Inbred C57BL,
pubmed-meshheading:7478538-Mice, Transgenic,
pubmed-meshheading:7478538-Precancerous Conditions,
pubmed-meshheading:7478538-Proto-Oncogene Proteins,
pubmed-meshheading:7478538-Proto-Oncogene Proteins c-bcl-2
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pubmed:year |
1995
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pubmed:articleTitle |
Survival and death of prelymphomatous B-cells from N-myc/bcl-2 double transgenic mice correlates with the regulation of intracellular Ca2+ fluxes.
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pubmed:affiliation |
Institut für Molekularbiologie und Tumorforschung, IMT, Philipps Universität Marburg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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