Manganese superoxide dismutase gene dosage affects chromosomal instability and tumor onset in a mouse model of T cell lymphoma

Christopher I van de Wetering; Mitchell C Coleman; Douglas R Spitz; Brian J Smith; C. Michael Knudson

doi:10.1016/j.freeradbiomed.2008.01.022

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Manganese superoxide dismutase gene dosage affects chromosomal instability and tumor onset in a mouse model of T cell lymphoma

Journal article

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Manganese superoxide dismutase gene dosage affects chromosomal instability and tumor onset in a mouse model of T cell lymphoma

Christopher I van de Wetering, Mitchell C Coleman, Douglas R Spitz, Brian J Smith and C. Michael Knudson

Free radical biology & medicine, Vol.44(8), pp.1677-1686

04/15/2008

DOI: 10.1016/j.freeradbiomed.2008.01.022

PMCID: PMC2374742

PMID: 18291119

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http://doi.org/10.1016/j.freeradbiomed.2008.01.022View

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Abstract

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 proapoptotic Bax. Lck-Bax38/1 transgenic mice were crossed to mice overexpressing MnSOD (Lck-MnSOD) as well as MnSOD+/− mice. The effects of MnSOD on apoptosis, cell cycle, chromosomal instability (CIN), and lymphoma development were 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 premalignant 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.

Bcl-2

Free radicals

MnSOD

ROS

Bax

Oncogenesis

Chromosomal instability

Apoptosis

Details

Title: Subtitle: Manganese superoxide dismutase gene dosage affects chromosomal instability and tumor onset in a mouse model of T cell lymphoma
Creators: Christopher I van de Wetering - Interdisciplinary Program in Molecular and Cellular Biology and Department of Pathology, University of Iowa, Iowa City, IA 52242, USA
Mitchell C Coleman - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA
Douglas R Spitz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA
Brian J Smith - College of Public Health, University of Iowa, Iowa City, IA 52242, USA
C. Michael Knudson - Interdisciplinary Program in Molecular and Cellular Biology and Department of Pathology, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Free radical biology & medicine, Vol.44(8), pp.1677-1686
DOI: 10.1016/j.freeradbiomed.2008.01.022
PMID: 18291119
PMCID: PMC2374742
NLM abbreviation: Free Radic Biol Med
ISSN: 0891-5849
eISSN: 1873-4596
Publisher: Elsevier Inc
Language: English
Date published: 04/15/2008
Academic Unit: Pathology; Biostatistics; Orthopedics and Rehabilitation; Radiation Oncology; Holden Comprehensive Cancer Center
Record Identifier: 9983997445802771

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