title: Manganese superoxide dismutase in breast cancer: from molecular mechanisms of gene regulation to biological and clinical significance.
abstract: Breast cancer is one of the most common malignancies of all cancers in women worldwide. Many difficulties reside in the prediction of tumor metastatic progression because of the lack of sufficiently reliable predictive biological markers, and this is a permanent preoccupation for clinicians. Manganese superoxide dismutase (MnSOD) may represent a rational candidate as a predictive biomarker of breast tumor metastatic progression, because its gene expression is profoundly altered between early and advanced breast cancer, in contrast to expression in the normal mammary gland. In this review, we report the characterization of some gene polymorphisms and molecular mechanisms of SOD2 gene regulation, which allows a better understanding of how MnSOD is decreased in early breast cancer and increased in advanced breast cancer. Several studies display the biological significance of MnSOD level in proliferation as well as in invasive and angiogenic abilities of breast tumor cells by controlling superoxide anion radical (O2(•-)) and hydrogen peroxide (H2O2). Particularly, they report how these reactive oxygen species may activate some signaling pathways involved in breast tumor growth. Emerging understanding of these findings provides an interesting framework for guiding translational research and suggests a way to define precisely the clinical interest of MnSOD as a prognostic and/or predicting marker in breast cancer, by associating with some regulators involved in SOD2 gene regulation and other well-known biomarkers, in addition to the typical clinical parameters.
authors.affiliation: Centre de Recherche en Automatique de Nancy, UMR 7039 CNRS, Faculté des Sciences et Technologies, Université de Lorraine, 54506 Vandoeuvre-lès-Nancy Cedex, France. Electronic address: philippe.becuwe@univ-lorraine.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Becuwe
authors.affiliation: Centre de Recherche en Automatique de Nancy, UMR 7039 CNRS, Faculté des Sciences et Technologies, Université de Lorraine, 54506 Vandoeuvre-lès-Nancy Cedex, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Ennen
authors.affiliation: Centre de Recherche en Automatique de Nancy, UMR 7039 CNRS, Faculté des Sciences et Technologies, Université de Lorraine, 54506 Vandoeuvre-lès-Nancy Cedex, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Klotz
authors.affiliation: Centre de Recherche en Automatique de Nancy, UMR 7039 CNRS, Faculté des Sciences et Technologies, Université de Lorraine, 54506 Vandoeuvre-lès-Nancy Cedex, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Barbieux
authors.affiliation: Centre de Recherche en Automatique de Nancy, UMR 7039 CNRS, Faculté des Sciences et Technologies, Université de Lorraine, 54506 Vandoeuvre-lès-Nancy Cedex, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Grandemange
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation; D004790:Enzyme Induction; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D013482:Superoxide Dismutase / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D013482:Superoxide Dismutase; D013481:Superoxides; D000099156:Superoxide Dismutase 2
keywords: Angiogenesis; Breast cancer; Free radicals; Gene regulation; Metastasis; MnSOD; Proliferation