SIRT3 is a Mitochondrial Tumor Suppressor and Genetic Loss Results in a Murine Model for ER/PR Positive Mammary Tumors Connecting Metabolism and Carcinogenesis
Abstract
The last year, which was funded by the DOD collaborative Breast Cancer Idea Award, has resulted in several important translational and basic science findings. Specifically, the most significant finding during the research period were: (1) the identification of MnSOD as a legitimate Sirt3 deacetylation target that for the first time shows that post-translation modifications of mitochondrial proteins plays a role in mitochondrial function (published in Molecular Cell); (2) that Sirt3 is first mitochondrial tumor suppressor protein that may play a role in the development of human luminal B breast malignancies; (3) that Sirt3 regulates the ATP synthase complex and the aberrant regulation of ATP synthase may play a role, at least in part, in breast carcinogenesis; (4) that tumors lacking Sirt3 may require the dysregulation of HIF-1 suggesting that there may be a subgroup of human tumors that may response to HIF-1 inhibitors in both chemoprevention as potentially as anti-cancer agents; and (5) that MnSOD function as both a molecular mechanism in breast cancers as well as the suggestion that agents that activate MnSOD may be agents for chemoprevention.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2011
- Accession Number
- ADA554224
Entities
People
- David Gius
- Sarki Abdulkadir
Organizations
- Vanderbilt University