Oncotarget

Research Papers:

Dual SIRT1 expression patterns strongly suggests its bivalent role in human breast cancer

Khaldoun Rifaï, Gaëlle Judes, Mouhamed Idrissou, Marine Daures, Yves-Jean Bignon, Frédérique Penault-Llorca and Dominique Bernard-Gallon _

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Oncotarget. 2017; 8:110922-110930. https://doi.org/10.18632/oncotarget.23006

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Abstract

Khaldoun Rifaï1,2, Gaëlle Judes1,2, Mouhamed Idrissou1,2, Marine Daures1,2, Yves-Jean Bignon1,2, Frédérique Penault-Llorca2,3 and Dominique Bernard-Gallon1,2

1Centre Jean Perrin, Department of Oncogenetics–CBRV, 63001 Clermont-Ferrand, France

2INSERM U 1240–IMoST, 63005 Clermont-Ferrand, France

3Centre Jean Perrin, Department of Biopathology, 63011 Clermont-Ferrand, France

Correspondence to:

Dominique Bernard-Gallon, email: dominique.gallon-bernard@clermont.unicancer.fr

Keywords: breast cancer; molecular subtypes; SIRT1; expression levels; statistical analysis

Received: July 08, 2017     Accepted: November 13, 2017     Published: December 06, 2017

ABSTRACT

Breast cancer is the most common cancer in women, and the leading cause of cancer death in women worldwide. SIRT1 (silent mating type information regulation 2 homolog) 1 is a class-III histone deacetylase involved in apoptosis regulation, DNA repair and tumorigenesis. However, its role in breast carcinoma remains controversial, as both tumor-suppressive and tumor-promoting functions have been reported. Also, there are very few reports available where expression of SIRT1 is comprehensively analyzed in breast tumors classified by molecular subtype. Here, using a cohort of 50 human breast tumors and their matched normal tissues, we investigated SIRT1 expression levels in the 5 molecular subtypes of breast cancer according to the St Gallen classification (2013). Tumors and their corresponding normal tissue samples were collected from all patients, and SIRT1 mRNA and protein expression levels were then examined by real-time quantitative polymerase chain reaction and immunoblotting, respectively. After statistical analysis, the results showed a dual expression profile of SIRT1 in human breast carcinoma, with significant overexpression in luminal and HER2-enriched subtypes and significantly reduced expression in the triple-negative subtype. We also found an inverse correlation between SIRT1 expression and breast cancer aggressivity. These novel findings suggest that SIRT1 plays a dual role in breast tumors depending on its expression rate and the molecular subtype of the cancer. Our data also point to a potential role for SIRT1 as a prognostic biomarker in breast cancer.


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