Manganese superoxide dismutase gene dosage affects chromosomal instability and tumor onset in a mouse model of T cell lymphoma
| Autor: | Mitchell C. Coleman, Douglas R. Spitz, C. Michael Knudson, Brian J. Smith, Christopher I. van de Wetering |
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| Rok vydání: | 2008 |
| Předmět: |
Genetically modified mouse
animal diseases Gene Dosage Apoptosis Mice Transgenic Biology Lymphoma T-Cell medicine.disease_cause Biochemistry Article Superoxide dismutase Mice Bcl-2-associated X protein Chromosomal Instability Physiology (medical) medicine Animals T-cell lymphoma Cell Proliferation bcl-2-Associated X Protein chemistry.chemical_classification Precursor Cells T-Lymphoid Reactive oxygen species Superoxide Dismutase Cell growth Cell Cycle fungi Cell cycle Aneuploidy medicine.disease Molecular biology Disease Models Animal Oxidative Stress enzymes and coenzymes (carbohydrates) chemistry biology.protein Reactive Oxygen Species Carcinogenesis |
| Zdroj: | Free Radical Biology and Medicine. 44:1677-1686 |
| ISSN: | 0891-5849 |
| Popis: | Increased reactive oxygen species (ROS) such as superoxide have been implicated as causal elements of oncogenesis. A variety of cancers have displayed changes in steady state levels of key antioxidant enzymes with the mitochondrial form of superoxide dismutase (MnSOD) being commonly implicated. Increasing MnSOD expression suppresses the malignant phenotype in various cancer cell lines and suppresses tumor formation in xenograft and transgenic mouse models. We examined the impact of MnSOD expression in the development of T cell lymphoma in mice expressing pro-apoptotic Bax. Lck-Bax38/1 transgenic mice were crossed to mice overexpressing MnSOD (Lck-MnSOD) as well as MnSOD +/− mice. The effect of MnSOD on apoptosis, cell cycle, chromosomal instability (CIN), and lymphoma development was determined. The apoptotic and cell cycle phenotypes observed in thymocytes from control and Bax transgenic mice were unaffected by variations in MnSOD levels. Remarkably, increased gene dosage of MnSOD significantly decreased aneuploidy in pre-malignant thymocytes as well as the onset of tumor formation in Lck-Bax38/1 mice. The observed effects of MnSOD support a role for ROS in CIN and tumor formation in this mouse model of T cell lymphoma. |
| Databáze: | OpenAIRE |
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