Author/Authors :
Kim، نويسنده , , Hyun-Seok and Patel، نويسنده , , Krish and Muldoon-Jacobs، نويسنده , , Kristi and Bisht، نويسنده , , Kheem S. and Aykin-Burns، نويسنده , , Nukhet and Pennington، نويسنده , , J. Daniel and van der Meer، نويسنده , , Riet and Nguyen، نويسنده , , Phuongmai and Savage، نويسنده , , Jason and Owens، نويسنده , , Kjerstin M. and Vassilopoulos، نويسنده , , Athanassios and Ozden، نويسنده , , Ozkan and Park، نويسنده , , Seong-Hoon and Singh، نويسنده , , Keshav K. and Abdulkadir، نويسنده , , Sarki A. and Spitz، نويسنده , , Douglas R. and Deng، نويسنده , , Chu-Xia and Gius، نويسنده , , David، نويسنده ,
Abstract :
Summary
rtuin 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.
