Mécanisme d'action de l'éthanol sur la prolifération et la migration des cellules cancéreuses mammaires MCF-7 : implication de la voie de signalisation des oestrogènes

Abstract : Many epidemiological studies have shown that chronic alcohol consumption increases significantly the incidence of breast cancer. Moreover, in vitro and in vivo studies show that ethanol can promote not only tumorogenesis but also tumor cells migration. These effects seem to be related to the hormone dependent status of breast cancer cells. The aim of our study was to elucidate the underlying molecular mechanisms by using the MCF-7 breast cancer cell line. First, we have confirmed that ethanol can stimulate the proliferation of these cells. We demonstrated that this effect is associated to an increase in the expression of ERa, COX-2 and aromatase, the enzyme responsible for estrogen synthesis. In contrast, other alcohols, such as methanol or butanol, decrease significantly the proliferation and do not increase the aromatase protein level. In the cell migration context, we have shown that ethanol stimulates the MMP-2 and MMP-9 secretion. This ethanol-induced increase in MMP-9 secretion is dependent of ERa activation. Ethanol could act not only by an increase in the local concentration of estrogens via aromatase overexpression, but also by an ERa ligand-independent activation that we have shown to be mediated by the AMPc/PKA signalling pathway and the A2a adenosine receptor. This receptor could be a new therapeutic target in the treatment of breast carcinoma.
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Nicolas Etique. Mécanisme d'action de l'éthanol sur la prolifération et la migration des cellules cancéreuses mammaires MCF-7 : implication de la voie de signalisation des oestrogènes. Sciences agricoles. Université Henri Poincaré - Nancy 1, 2006. Français. ⟨NNT : 2006NAN10144⟩. ⟨tel-01754302⟩

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