FoxO3 suppresses Myc-driven lymphomagenesis
- Author(s)
- Vandenberg, CJ; Motoyama, N; Cory, S;
- Journal Title
- Cell Death Dis
- Publication Type
- Journal Article
- Abstract
- 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 Emu-myc transgenic mice. Tumour analysis indicated that the selective pressure for mutation of the p53 pathway during Emu-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(-/-)Emu-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.
- Publisher
- NPG
- Research Division(s)
- Molecular Genetics Of Cancer
- PubMed ID
- 26764572
- Publisher's Version
- https://doi.org/10.1038/cddis.2015.396
- NHMRC Grants
- NHMRC/461221, NHMRC/1016647,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-01-29 11:46:11
Last Modified: 2016-01-29 02:18:17