| First Author | Michalak EM | Year | 2010 |
| Journal | Genes Dev | Volume | 24 |
| Issue | 15 | Pages | 1608-13 |
| PubMed ID | 20679396 | Mgi Jnum | J:163252 |
| Mgi Id | MGI:4821500 | Doi | 10.1101/gad.1940110 |
| Citation | Michalak EM, et al. (2010) Apoptosis-promoted tumorigenesis: gamma-irradiation-induced thymic lymphomagenesis requires Puma-driven leukocyte death. Genes Dev 24(15):1608-13 |
| abstractText | Although tumor development requires impaired apoptosis, we describe a novel paradigm of apoptosis-dependent tumorigenesis. Because DNA damage triggers apoptosis through p53-mediated induction of BH3-only proteins Puma and Noxa, we explored their roles in gamma-radiation-induced thymic lymphomagenesis. Surprisingly, whereas Noxa loss accelerated it, Puma loss ablated tumorigenesis. Tumor suppression by Puma deficiency reflected its protection of leukocytes from gamma-irradiation-induced death, because their glucocorticoid-mediated decimation in Puma-deficient mice activated cycling of stem/progenitor cells and restored thymic lymphomagenesis. Our demonstration that cycles of cell attrition and repopulation by stem/progenitor cells can drive tumorigenesis has parallels in human cancers, such as therapy-induced malignancies. |
