Functional antagonism between pro-apoptotic BIM and anti-apoptotic BCL-XL in MYC-induced lymphomagenesis.
- Author(s)
- Delbridge, AR; Grabow, S; Bouillet, P; Adams, JM; Strasser, A;
- Details
- Publication Year 2015-04,Volume 34,Issue #14,Page 1872-6
- Journal Title
- Oncogene
- Publication Type
- JOURNAL ARTICLE
- Abstract
- Genomic analyses revealed that many cancers have acquired abnormalities in their expression of pro- or anti-apoptotic members of the BCL-2 protein family. It is, however, unknown whether changes in pro- or anti-apoptotic BCL-2 family members have similar impact on tumorigenesis or whether changes in one subgroup have disproportionate impact. We compared the consequences of concomitant loss of anti-apoptotic Bclx and pro-apoptotic Bim on MYC-induced lymphomagenesis. Whereas only loss of both Bclx alleles markedly forestalled tumorigenesis, loss of a single Bim allele overcame this blockade. Conversely, loss of even a single Bim allele sufficed to substantially accelerate lymphomagenesis, and only loss of both but not loss of a single allele of Bclx could attenuate this acceleration. The evidence that modest (two-fold) monoallelic changes in the expression of at least some BH3-only proteins can profoundly impact tumorigenesis suggests that such aberrations, imposed by epigenetic or genetic changes, may expedite tumorigenesis more effectively than elevated expression of pro-survival BCL-2 family members. These findings further our understanding of the mechanisms of lymphomagenesis and possibly also cancer therapy.Oncogene advance online publication, 26 May 2014; doi:10.1038/onc.2014.132.
- Publisher
- NPG
- Research Division(s)
- Molecular Genetics Of Cancer
- PubMed ID
- 24858047
- Publisher's Version
- https://doi.org/10.1038/onc.2014.132
- NHMRC Grants
- NHMRC/461221, NHMRC/1016701, NHMRC/1020363, NHMRC/1046010,
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Creation Date: 2014-05-28 07:35:44
Last Modified: 2015-11-11 11:45:35