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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1995-12-28
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2165-74
pubmed:dateRevised
2006-11-15
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
pubmed:year
1995
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.
pubmed:affiliation
Institut für Molekularbiologie und Tumorforschung, IMT, Philipps Universität Marburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't