Identification of Sirtuin 3, a mitochondrial protein deacetylase, as a new contributor to tamoxifen resistance in breast cancer cells.
Biochem Pharmacol
; 86(6): 726-33, 2013 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-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 ERß, 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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Tamoxifeno
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Neoplasias da Mama
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Regulação Neoplásica da Expressão Gênica
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Resistencia a Medicamentos Antineoplásicos
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Antineoplásicos Hormonais
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Sirtuína 3
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Mitocôndrias
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article