| Literature DB >> 20129246 |
Hyun-Seok Kim1, Krish Patel, Kristi Muldoon-Jacobs, Kheem S Bisht, Nukhet Aykin-Burns, J Daniel Pennington, Riet van der Meer, Phuongmai Nguyen, Jason Savage, Kjerstin M Owens, Athanassios Vassilopoulos, Ozkan Ozden, Seong-Hoon Park, Keshav K Singh, Sarki A Abdulkadir, Douglas R Spitz, Chu-Xia Deng, David Gius.
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. Copyright (c) 2010 Elsevier Inc. All rights reserved.Entities:
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Year: 2010 PMID： 20129246 PMCID： PMC3711519 DOI： 10.1016/j.ccr.2009.11.023
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743