Journal article
Identification of Sirtuin 3, a mitochondrial protein deacetylase, as a new contributor to tamoxifen resistance in breast cancer cells
Biochemical Pharmacology, Vol.86(6), pp.726-733
09/15/2013
DOI: 10.1016/j.bcp.2013.06.032
PMID: 23856293
Abstract
The current study reports a previously unappreciated role of Sirtuin 3 (SIRT3), a mitochondrial protein deacetylase, in altering sensitivity of breast cancer cells to tamoxifen (Tam), a commonly used anti-estrogen agent. We showed that SIRT3 was significantly up-regulated at both mRNA and protein levels in the Tam-resistance human breast cancer cell line MTR-3, which was derived from MCF-7 line by continuous selective culture in the presence of 1μM of Tam for two years. We further demonstrated that SIRT3 was rapidly up-regulated in the sensitive MCF-7 cells following exposure to Tam. Transfection of MCF-7 cells with a SIRT3 expression plasmid decreased cellular sensitivity to Tam and blocked the Tam-induced apoptosis. Furthermore, silencing of SIRT3 expression in MTR-3 cells sensitized the resistant cells to Tam and enhanced apoptotic cell death. MTR-3 cells with silencing of SIRT3 expression showed increases in the mitochondrial content of ERβ, ROS level and apoptosis. These results not only uncovered a new role for SIRT3 in cancer but also identified this mitochondrial protein deacetylase as a previously unrecognized factor that participates in regulation of Tam sensitivity in breast cancer cells. Thus, SIRT3 might be considered as a potential target for overcoming Tam resistance in treatment of breast cancer.
Details
- Title: Subtitle
- Identification of Sirtuin 3, a mitochondrial protein deacetylase, as a new contributor to tamoxifen resistance in breast cancer cells
- Creators
- Li Zhang - Department of Pharmacology and The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United StatesXingcong Ren - Department of Pharmacology and The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United StatesYan Cheng - Department of Pharmacology and The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United StatesKathryn Huber-Keener - Department of Pharmacology and The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United StatesXiuping Liu - The University of Texas MD Anderson Cancer CenterYi Zhang - Penn State Milton S. Hershey Medical CenterYun-Sheng Yuan - Department of Pharmacology and The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United StatesJay W Yang - Penn State Milton S. Hershey Medical CenterChang-Gong Liu - Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX 77584, United StatesJin-Ming Yang - Department of Pharmacology and The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United States
- Resource Type
- Journal article
- Publication Details
- Biochemical Pharmacology, Vol.86(6), pp.726-733
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.bcp.2013.06.032
- PMID
- 23856293
- ISSN
- 0006-2952
- eISSN
- 1873-2968
- Language
- English
- Date published
- 09/15/2013
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9983931014502771
Metrics
23 Record Views