期刊
ONCOGENE
卷 34, 期 14, 页码 1872-1876出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2014.132
关键词
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资金
- National Health and Medical Research Council of Australia [461221/1016701, 1020363, 1046010]
- Leukemia and Lymphoma Society [7413, 7001-13]
- Cancer Council Victoria (CCV) [1052309]
- Cancer Council of Victoria
- Lady Tata Postdoctoral Fellowship
- Melbourne International Research Scholarship (University of Melbourne)
- Melbourne International Fee Remission Scholarship (University of Melbourne)
- Australian Postgraduate Award
- Cancer Therapeutics CRC Top-up Scholarship
- Australian Government (IRISS)
- Victorian State Government (OIS)
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.
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