Role of manganese superoxide dismutase on growth and invasive properties of human estrogen-independent breast cancer cells.
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.
Kattan
Zilal
Z
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.
Minig
Vanessa
V
Leroy
Pierre
P
Dauça
Michel
M
Becuwe
Philippe
P
D000975:Antioxidants / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D004967:Estrogens / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D061105:Peroxiredoxin III; D054464:Peroxiredoxins / Q000378:metabolism; D016372:RNA, Antisense / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D000099156:Superoxide Dismutase 2
D000975:Antioxidants; D002374:Catalase; D004967:Estrogens; D006861:Hydrogen Peroxide; D020780:Matrix Metalloproteinase 9; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D016372:RNA, Antisense; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C516115:PRDX3 protein, human