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

• Published in: Breast cancer research and treatment Vol. 108; no. 2; pp. 203 - 215
• Main Authors: Kattan, Zilal, Minig, Vanessa, Leroy, Pierre, Dauça, Michel, Becuwe, Philippe
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-03-2008; Springer; Springer Nature B.V
• Subjects: Antioxidants - pharmacology; Biological and medical sciences; Breast cancer; Breast Neoplasms - enzymology; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer research; Cancer therapies; Catalase - metabolism; Cell growth; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Down-Regulation; Enzymes; Estrogens; Estrogens - metabolism; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Hydrogen Peroxide - metabolism; Mammary gland diseases; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Medicine; Medicine & Public Health; Neoplasm Invasiveness; Oncology; Pathology; Peroxiredoxin III; Peroxiredoxins - metabolism; Preclinical Study; RNA, Antisense - metabolism; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Time Factors; Transfection; Tumors; Cell growth; Reactive oxygen species; Matrix metalloproteinases; Invasiveness; Breast cancer; Metastasis; Manganese superoxide dismutase; Human; Cell proliferation; Oxidative stress; Breast disease; Enzyme; Growth; Estrogen; Manganese superoxide dismutase, Breast cancer, Cell growth, Invasiveness, Metastasis; Metalloendopeptidases; Superoxide dismutase; Malignant tumor; Ovarian hormone; Mammary gland diseases; Peptidases; Hydrolases; Oxidoreductases; Sex steroid hormone; Tumor cell; Cancer
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-007-9597-5

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 (H
2
O
2
) and by a low expression of the major H
2
O
2
-detoxifying enzymes, catalase, and peroxiredoxin 3, compared to MCF-7 cells. Suppression of MnSOD expression by antisense RNA was associated with a decrease of H
2
O
2
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 H
2
O
2
scavengers markedly reduced tumor cell growth and colony formation. In addition, MnSOD suppression or treatment with H
2
O
2
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 H
2
O
2
production. In addition, these results suggest that MnSOD up-regulation may be one mechanism that contributes to the development of metastatic breast cancers.