Apoptosis-promoted tumorigenesis: gamma-irradiation-induced thymic lymphomagenesis requires Puma-driven leukocyte death
Details
Publication Year 2010-08-01, Volume 24, Issue #15, Page 1608-1613
Journal Title
GENES & DEVELOPMENT
Publication Type
Journal Article
Abstract
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.
Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
Keywords
PROTECTS HEMATOPOIETIC STEM; BH3-ONLY PROTEINS PUMA; PROAPOPTOTIC GENE; TRANSGENIC MICE; CANCER-CELLS; BCL-2 FAMILY; P53; RADIATION; DELETION; THERAPY
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2010-08-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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