Abstract
Mammalian Sirtuins have been shown to perform distinct cellular functions and deregulated expression of these genes was reported to be involved in the development of various malignancies including breast cancer. An increasing number of evidence indicates that Sirtuins have both tumor promoter and tumor suppressor functions. However, the roles of Sirtuins have not been well-studied in breast cancer. In the present study, quantitative expression levels of Sirtuins (SIRT1-3) together with a set of cancer related genes (cMYC, P53, SOD and HIF-1α genes) were assessed in malignant breast cancer and non-malignant control samples by using a high-throughput real-time PCR method. As a result, Sirtuins were found to be differentially expressed in breast cancer tissues and control samples, respectively. Particularly, expressions of SIRT1 (p = 0.035) and SIRT3 (p = 0.033) were found to be significantly up regulated, whereas SIRT2 (p = 0.032) gene was shown to be downregulated in breast cancer tissues compared to control samples in our study. Additionally, the expression levels of SIRT1-3 genes were correlated to both the selected cancer related genes and to clinicopathological parameters of breast cancer patients. In conclusion, SIRT1 and SIRT3 genes may act as oncogenes, whereas SIRT2 gene may operate as a tumor suppressor gene in human breast cancer.
Highlights
Breast cancer, as other cancers, has an unstable genome which generates the genetic diversity through deregulation of gene expression profiles and disruption of molecular networks (Hanahan and Weinberg, 2011)
SIRT1-3, members of Class III histone deacetylases of sirtuin family, are related to epigenetic regulatory proteins that are capable of deacetylation chromatin proteins, which are key elements in the regulation of gene expression, and of non-histone proteins leading to inappropriate activation or inhibition of various cellular signaling pathways (Minucci and Pelicci, 2006; Sandoval and Esteller, 2012)
We aimed to investigate the mRNA expressions of SIRT1-3 genes and a set of cancer related genes like cMYC, P53, Superoxide Dismutase (SOD) and HIF-1α in human breast cancer
Summary
As other cancers, has an unstable genome which generates the genetic diversity through deregulation of gene expression profiles and disruption of molecular networks (Hanahan and Weinberg, 2011). Class III Histone Deacetylases (HDACs), are a family of proteins composed of 7 members, including SIRT1-7 which are evolutionary conserved enzymes homologous with the yeast Sir family of proteins (Landry et al, 2000). They are Nicotinamide Adenine Dinucleotide (NAD+) dependent deacetylases and/or mono-Adenosine Diphosphate (ADP)-ribosyl transferases that have attracted tremendous attention as stress adaptors and posttranslational modifiers and they have been linked to many diseases including cancer (Bosch-Presegué and Vaquero; 2011).
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