FoxO3 suppresses Myc-driven lymphomagenesis
AuthorVandenberg, CJ; Motoyama, N; Cory, S
Source TitleCell Death and Disease
PublisherNATURE PUBLISHING GROUP
AffiliationMedical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsVandenberg, C. J., Motoyama, N. & Cory, S. (2016). FoxO3 suppresses Myc-driven lymphomagenesis. CELL DEATH & DISEASE, 7 (1), https://doi.org/10.1038/cddis.2015.396.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816178
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 Eμ-myc transgenic mice. Tumour analysis indicated that the selective pressure for mutation of the p53 pathway during Eμ-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(-/-)Eμ-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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