Whole body fluorescence imaging of lymphoma progression in live mice. The cover shows the temporal and spatial progression of Em-myc lymphoma cells tagged with green fluorescent protein in a live mouse (with time progression from top to bottom). Note that the lymphomas first expand within the lympoid compartments and bone. In the absence of p53 or following Bcl-2 overexpression, these lympomas readily disseminate into nonlympoid compartments. For details see Schmitt et al. (pp. 289-298) in this issue. |
Summary: Although the p53 tumor supressor acts in
plethora of processes that influence cellular proliferation and
survival, it remains unclear which p53 functions are essential for tumor
suppression and, as a consequence, are selected against during tumor
development. Using a mouse model harbouring primary, genetically
modified myc-driven lympomas, we show that disruption of apoptosis
downstream of p53 by Bcl2 or a dominant-negative caspase 9 confers-like
p53 loss-a selective advantage, and completely alleviates pressure to
inactivate p53 during lymphomagenesis. Despite their p53-null-like
aggressive phenotype, apoptosis-defective lymphomas that retain intact
p53 genes do not display the checkpoint defects and gross aneuploidy
that are charcteristic of p53 mutant tumors. Therefore, apoptosis is the
only p53 function selected against during lymphoma development, whereas
defective cell-cycle checkpoints and aneuploidy are mere byproducts of
p53 loss.
Figure 4. Whole body fluorescence imaging allows visualisation of lymphoma dissemination.
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