| Apoptosis of leukocytes triggered by acute DNA damage promotes lymphoma formation. | |
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MedLine Citation:
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PMID: 20679395 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Apoptosis triggered by p53 upon DNA damage secures removal of cells with compromised genomes, and is thought to prevent tumorigenesis. In contrast, we provide evidence that p53-induced apoptosis can actively drive tumor formation. Mice defective in p53-induced apoptosis due to loss of its proapoptotic target gene, puma, resist gamma-irradiation (IR)-induced lymphomagenesis. In wild-type animals, repeated irradiation injury-induced expansion of hematopoietic stem/progenitor cells (HSCs) leads to lymphoma formation. Puma(-/-) HSCs, protected from IR-induced cell death, show reduced compensatory proliferation and replication stress-associated DNA damage, and fail to form thymic lymphomas, demonstrating that the maintenance of stem/progenitor cell homeostasis is critical to prevent IR-induced tumorigenesis. |
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Authors:
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Verena Labi; Miriam Erlacher; Gerhard Krumschnabel; Claudia Manzl; Alexandar Tzankov; Josephina Pinon; Alexander Egle; Andreas Villunger |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Genes & development Volume: 24 ISSN: 1549-5477 ISO Abbreviation: Genes Dev. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-03 Completed Date: 2010-08-17 Revised Date: 2011-07-22 |
Medline Journal Info:
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Nlm Unique ID: 8711660 Medline TA: Genes Dev Country: United States |
Other Details:
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Languages: eng Pagination: 1602-7 Citation Subset: IM |
Affiliation:
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Division of Developmental Immunology, Biocenter, Innsbruck Medical University, Innsbruck 6020, Austria. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis* / genetics Apoptosis Regulatory Proteins / genetics, metabolism Cell Proliferation DNA Damage* / radiation effects DNA Replication Gamma Rays Hematopoietic Stem Cells / cytology, radiation effects Leukocytes / pathology*, radiation effects Lymphoma / genetics, physiopathology* Mice Mice, Knockout T-Lymphocytes / cytology, physiology Tumor Suppressor Protein p53 / metabolism Tumor Suppressor Proteins / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Regulatory Proteins; 0/PUMA protein, mouse; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins |
| Comments/Corrections | |
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