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Breast Cancer Research and Treatment

Erschienen in:

01.03.2008 | Preclinical Study

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

verfasst von: Zilal Kattan, Vanessa Minig, Pierre Leroy, Michel Dauça, Philippe Becuwe

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2008

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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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Titel: Role of manganese superoxide dismutase on growth and invasive properties of human estrogen-independent breast cancer cells
verfasst von: Zilal Kattan
Vanessa Minig
Pierre Leroy
Michel Dauça
Philippe Becuwe
Publikationsdatum: 01.03.2008
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2008
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-007-9597-5

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