Survival and death of prelymphomatous B-cells from N-myc/bcl-2 double transgenic mice correlates with the regulation of intracellular Ca2+ fluxes.
Oncogene
; 11(10): 2165-74, 1995 Nov 16.
Article
in En
| MEDLINE
| ID: mdl-7478538
ABSTRACT
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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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Precancerous Conditions
/
B-Lymphocytes
/
Calcium
/
Genes, myc
/
Lymphoma, B-Cell
/
Proto-Oncogene Proteins
/
Apoptosis
Limits:
Animals
Language:
En
Journal:
Oncogene
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
1995
Document type:
Article
Affiliation country:
Germany