Journal article
SIRT3 Is a Mitochondria-Localized Tumor Suppressor Required for Maintenance of Mitochondrial Integrity and Metabolism during Stress
Cancer cell, Vol.17(1), pp.41-52
2010
DOI: 10.1016/j.ccr.2009.11.023
PMID: 20129246
Abstract
The sirtuin gene family (
SIRT) is hypothesized to regulate the aging process and play a role in cellular repair. This work demonstrates that SIRT3
−/− mouse embryonic fibroblasts (MEFs) exhibit abnormal mitochondrial physiology as well as increases in stress-induced superoxide levels and genomic instability. Expression of a single oncogene (
Myc or
Ras) in SIRT3
−/− MEFs results in in vitro transformation and altered intracellular metabolism. Superoxide dismutase prevents transformation by a single oncogene in SIRT3
−/− MEFs and reverses the tumor-permissive phenotype as well as stress-induced genomic instability. In addition, SIRT3
−/− mice develop ER/PR-positive mammary tumors. Finally, human breast and other human cancer specimens exhibit reduced
SIRT3 levels. These results identify
SIRT3 as a genomically expressed, mitochondria-localized tumor suppressor.
► SIRT3 is a genomically expressed, mitochondrial-localized in vitro tumor suppressor ► Mice lacking SIRT3 develop ER/PR-positive invasive ductal mammary tumors ► SIRT3 is decreased in human breast cancer tumors and several other malignancies ► SIRT3 loss results in aberrant mitochondrial metabolism and genomic instability
Details
- Title: Subtitle
- SIRT3 Is a Mitochondria-Localized Tumor Suppressor Required for Maintenance of Mitochondrial Integrity and Metabolism during Stress
- Creators
- Hyun-Seok Kim - Genetics of Development and Disease Branch, NIDDK, NIH, Bethesda, MD 20892, USAKrish Patel - Molecular Radiation Oncology, Radiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USAKristi Muldoon-Jacobs - Molecular Radiation Oncology, Radiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USAKheem S Bisht - Molecular Radiation Oncology, Radiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USANukhet Aykin-Burns - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USAJ. Daniel Pennington - Molecular Radiation Oncology, Radiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USARiet van der Meer - Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USAPhuongmai Nguyen - Molecular Radiation Oncology, Radiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USAJason Savage - Molecular Radiation Oncology, Radiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USAKjerstin M Owens - Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USAAthanassios Vassilopoulos - Genetics of Development and Disease Branch, NIDDK, NIH, Bethesda, MD 20892, USAOzkan Ozden - Molecular Radiation Oncology, Radiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USASeong-Hoon Park - Molecular Radiation Oncology, Radiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USAKeshav K Singh - Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USASarki A Abdulkadir - Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USADouglas R Spitz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USAChu-Xia Deng - Genetics of Development and Disease Branch, NIDDK, NIH, Bethesda, MD 20892, USADavid Gius - Molecular Radiation Oncology, Radiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA
- Resource Type
- Journal article
- Publication Details
- Cancer cell, Vol.17(1), pp.41-52
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.ccr.2009.11.023
- PMID
- 20129246
- ISSN
- 1535-6108
- eISSN
- 1878-3686
- Language
- English
- Date published
- 2010
- Academic Unit
- Pathology; Radiation Oncology
- Record Identifier
- 9984046814902771
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