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L'expression du gène mdr-1 est-elle régulée par le cycle de la méthionine

Abstract : Multidrug resistance stands as a major obstacle to efficient chemotherapy. The present work shows that the methioninecycle is capable of regulating the multidrug resistance phenomenon (MDR) in the HepG2 cellline. It highlights a pathway through which cobalamine (which is the cofactor of Methionine-Synthase) represses the mdr-1 gene which is the most commonly adressed MOR mediator. This work decribes the changes induced by cobalamine in the S-AdenosyIMethioninejS-AdenosylHomocysteine ratio, in the methylation process which converts PhosphatidylEthanolamine into PhosphatidylCholine, and in the Phospholipase D activity. These changes are corelated to changes induced by cobalamine in mdr-1 gene expression as well as in Pgp (encoded by mdr-1) expression and function. We also address a coregulation mechanism between cox-2 and mdr-1, which also operates in this pathway. This analysis suggests a possible new and concrete approach ih circumventing resistance to anticancerous agents su ch as vinblastine or doxorubicine through the use of cobalamine, phospholipase 0 activators or Cox-2 inhibitors in HepG2 cells.
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Submitted on : Thursday, March 29, 2018 - 10:49:30 AM
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  • HAL Id : tel-01747013, version 1



Véronique Marguerite. L'expression du gène mdr-1 est-elle régulée par le cycle de la méthionine. Biotechnologies. Université Henri Poincaré - Nancy 1, 2007. Français. ⟨NNT : 2007NAN10158⟩. ⟨tel-01747013⟩



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