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2016 ; 6
(1
): e2046
Nephropedia Template TP
Cell Death Dis
2016[Jan]; 6
(1
): e2046
PMID26764572
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This study demonstrates, for the first time, that loss of a single forkhead box
class O (FoxO) transcription factor, can promote lymphomagenesis. Using two
different mouse models, we show that FoxO3 has a significant tumour-suppressor
function in the context of Myc-driven lymphomagenesis. Loss of FoxO3
significantly accelerated myeloid tumorigenesis in vavP-MYC10 transgenic mice and
B lymphomagenesis in E?-myc transgenic mice. Tumour analysis indicated that the
selective pressure for mutation of the p53 pathway during E?-myc lymphomagenesis
was not altered. Frank tumours were preceded by elevated macrophage numbers in
FoxO3(-/-) vavP-MYC10 mice but, surprisingly, pre-B-cell numbers were relatively
normal in healthy young FoxO3(-/-)E?-myc mice. In vitro assays revealed enhanced
survival capacity of Myc-driven cells lacking FoxO3, but no change in cell
cycling was detected. The loss of FoxO3 may also be affecting other
tumour-suppressive functions for which FoxO1/4 cannot fully compensate.
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