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Role of manganese superoxide dismutase on growth and invasive properties of human estrogen-independent breast cancer cells

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Abstract

Manganese superoxide dismutase (MnSOD) is known to play a role in cancer. MnSOD exerts a tumor suppressive effect in estrogen-dependent human breast cancer cells. In the present study we investigated the in vitro role of MnSOD in the growth of some aggressive and highly metastatic estrogen-independent breast cancer cells, i.e., MDA-MB231 and SKBR3 cells. We show that estrogen-independent cells expressed a significantly higher basal MnSOD level compared to estrogen-dependent human breast cancer cell lines (MCF-7 and T47D). For MDA-MB231 cells, the high-MnSOD level was accompanied by an overproduction of intracellular hydrogen peroxide (H2O2) and by a low expression of the major H2O2-detoxifying enzymes, catalase, and peroxiredoxin 3, compared to MCF-7 cells. Suppression of MnSOD expression by antisense RNA was associated with a decrease of H2O2 content and caused a stimulation of growth with a reduced cell doubling time but induced a decrease of colony formation. Furthermore, treatment of MDA-MB231 cells with H2O2 scavengers markedly reduced tumor cell growth and colony formation. In addition, MnSOD suppression or treatment with H2O2 scavengers reduced the invasive properties of MDA-MB231 cells up to 43%, with a concomitant decrease of metalloproteinase-9 activity. We conclude that MnSOD plays a role in regulating tumor cell growth and invasive properties of estrogen-independent metastatic breast cancer cells. These action are mediated by MnSOD-dependent H2O2 production. In addition, these results suggest that MnSOD up-regulation may be one mechanism that contributes to the development of metastatic breast cancers.

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Acknowledgments

The authors are grateful to E. Brunner and L. Tirand for their skillful technical assistance, to Professor J. L. Merlin (Centre Alexis Vautrin, Vandoeuvre lès Nancy, France) for the gift of breast cancer cell lines, and to Dr. A. Taube for critical reading of the manuscript. This work was supported by grants from the Ligue contre le Cancer (Comité de Meuse), Association pour la Recherche sur le Cancer and the Université Henri Poincaré-Nancy I. Z. Kattan and V. Minig have a fellowship from Syrian Government and the Ligue contre le Cancer (Comité de Meurthe et Moselle), respectively. Z. Kattan and V. Minig contributed equally to this work.

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Authors and Affiliations

  1. Laboratoire de Biologie Cellulaire du Développement, EA 3446-IFR111 (Proliférateurs de Peroxysomes), Université Henri Poincaré-Nancy I, Faculté des Sciences, B.P. 239, 54506, Vandoeure-les-Nancy, France

    Zilal Kattan, Vanessa Minig, Michel Dauça & Philippe Becuwe

  2. Laboratoire de Chimie Physique et Microbiologie pour l’Environnement, UMR 7564 CNRS Nancy-Université, Faculté de Pharmacie, B.P. 80403, 54001, Nancy, France

    Pierre Leroy

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  1. Zilal Kattan
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  2. Vanessa Minig
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  4. Michel Dauça
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Correspondence to Philippe Becuwe.

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Kattan, Z., Minig, V., Leroy, P. et al. Role of manganese superoxide dismutase on growth and invasive properties of human estrogen-independent breast cancer cells. Breast Cancer Res Treat 108, 203–215 (2008). https://doi.org/10.1007/s10549-007-9597-5

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