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Sirt3 Exerts Its Tumor-Suppressive Role by Increasing p53 and Attenuating Response to Estrogen in MCF-7 Cells

Pinterić, Marija; Podgorski, Iva I.; Popović Hadžija, Marijana; Filić, Vedrana; Paradžik, Mladen; Proust, Bastien Lucien Jean; Dekanić, Ana; Ciganek, Ivan; Pleše, Denis; Marčinko, Dora; Balog, Tihomir; Sobočanec, Sandra (2020) Sirt3 Exerts Its Tumor-Suppressive Role by Increasing p53 and Attenuating Response to Estrogen in MCF-7 Cells. Antioxidants, 9 (4). ISSN 2076-3921

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Estrogen (E2) is a major risk factor for the initiation and progression of malignancy in estrogen receptor (ER) positive breast cancers, whereas sirtuin 3 (Sirt3), a major mitochondrial NAD+-dependent deacetylase, has the inhibitory effect on the tumorigenic properties of ER positive MCF-7 breast cancer cells. Since it is unclear if this effect is mediated through the estrogen receptor alpha (ERα) signaling pathway, in this study, we aimed to determine if the tumor-suppressive function of Sirt3 in MCF-7 cells interferes with their response to E2. Although we found that Sirt3 improves the antioxidative response and mitochondrial fitness of the MCF-7 cells, it also increases DNA damage along with p53, AIF, and ERα expression. Moreover, Sirt3 desensitizes cells to the proliferative effect of E2, affects p53 by disruption of the ERα–p53 interaction, and decreases proliferation, colony formation, and migration of the cells. Our observations indicate that these tumor-suppressive effects of Sirt3 could be reversed by E2 treatment only to a limited extent which is not sufficient to recover the tumorigenic properties of the MCF-7 cells. This study provides new and interesting insights with respect to the functional role of Sirt3 in the E2-dependent breast cancers.

Item Type: Article
Uncontrolled Keywords: sirtuin 3; MCF-7; estrogen receptor; p53; breast cancer cells
NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
Divisions: Division of Molecular Biology
Division of Molecular Medicine
Project titleProject leaderProject codeProject type
Sirtuin3 kao posrednik mitohondrijske funkcije u estrogen-ovisnoj otpornosti na oksidativni stres i prehranu s visokim udjelom masti-SuMERATihomir BalogIP-2014-09-4533HRZZ
Depositing User: Iva Škrinjar
Date Deposited: 10 Apr 2020 12:40
DOI: 10.3390/antiox9040294

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