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Catalase expression in MCF-7 breast cancer cells is mainly controlled by PI3K/Akt/mTor signaling pathway.
Glorieux, Christophe; Auquier, Julien; Dejeans, Nicolas; Sid, Brice; Demoulin, Jean-Baptiste; Bertrand, Luc; Verrax, Julien; Calderon, Pedro Buc.
Afiliación
  • Glorieux C; Université catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group, Brussels, Belgium.
  • Auquier J; Université catholique de Louvain, Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Brussels, Belgium.
  • Dejeans N; Université Bordeaux-Segalen, Inserm U1053, Bordeaux, France.
  • Sid B; Université catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group, Brussels, Belgium.
  • Demoulin JB; Université catholique de Louvain, de Duve Institute, Experimental Medicine Unit, Brussels, Belgium.
  • Bertrand L; Université catholique de Louvain, Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Brussels, Belgium.
  • Verrax J; Université catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group, Brussels, Belgium.
  • Calderon PB; Université catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group, Brussels, Belgium; Facultad de Ciencias de la Salud, Universidad Arturo Prat, Iquique, Chile. Electronic address: pedro.buccalderon@uclouvain.be.
Biochem Pharmacol ; 89(2): 217-23, 2014 May 15.
Article en En | MEDLINE | ID: mdl-24630930
Catalase is an antioxidant enzyme that catalyzes mainly the transformation of hydrogen peroxide into water and oxygen. Although catalase is frequently down-regulated in tumors the underlying mechanism remains unclear. Few transcription factors have been reported to directly bind the human catalase promoter. Among them FoxO3a has been proposed as a positive regulator of catalase expression. Therefore, we decided to study the role of the transcription factor FoxO3a and the phosphatidylinositol-3 kinase (PI3K) signaling pathway, which regulates FoxO3a, in the expression of catalase. To this end, we developed an experimental model of mammary breast MCF-7 cancer cells that acquire resistance to oxidative stress, the so-called Resox cells, in which catalase is overexpressed as compared with MCF-7 parental cell line. In Resox cells, Akt expression is decreased but its phosphorylation is enhanced when compared with MCF-7 cells. A similar profile is observed for FoxO3a, with less total protein but more phosphorylated FoxO3a in Resox cells, correlating with its higher Akt activity. The modulation of FoxO3a expression by knockdown and overexpression strategies did not affect catalase expression, neither in MCF-7 nor in Resox cells. Inhibition of PI3K and mTOR by LY295002 and rapamycin, respectively, decreases the phosphorylation of downstream targets (i.e. GSK3ß and p70S6K) and leads to an increase of catalase expression only in MCF-7 but not in Resox cells. In conclusion, FoxO3a does not appear to play a critical role in the regulation of catalase expression in both cancer cells. Only MCF-7 cells are sensitive and dependent on PI3K/Akt/mTOR signaling.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Catalasa / Regulación Enzimológica de la Expresión Génica / Proteínas Proto-Oncogénicas c-akt / Fosfatidilinositol 3-Quinasa / Serina-Treonina Quinasas TOR Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Biochem Pharmacol Año: 2014 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Catalasa / Regulación Enzimológica de la Expresión Génica / Proteínas Proto-Oncogénicas c-akt / Fosfatidilinositol 3-Quinasa / Serina-Treonina Quinasas TOR Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Biochem Pharmacol Año: 2014 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido