Skip to Main content Skip to Navigation
Theses

Voies de signalisation cobalamine-dépendantes de l'expression du gène MDR-1. Une cible pharmacologique nouvelle pour la chimiothérapie ?

Abstract : A key factor of chemioresistance is an increased expression of MDR-1 gene, partly controlled by cellular methylation reactions. Until now, the physiology of these reactions is not clearly known. The main intracellular metabolic pathway, generating methyl donors, is the methionine cycle, the activity of which is strongly depending on B-group vitamins (B12, B9). Thus, MDR-1 gene expression may be controlled by the activity of the methionine cycle and consequently presence of these vitamins. The aim of this study is to determine if, and to elucidate how, the methionine cycle influences the MDR-1 gene expression. Chromatography, pharmacotoxicology, cell culture techniques, gene and protein expression studies have been used on the human hepatocarcinoma cell line HepG2. We showed that cobalamin-induced MDR-1 gene repression was associated with phospholipase D activation, Akt phosphorylation, and Cox-2 co-repression in a complex and intricated manner. We may suggest that targeting these pathways could potentiate chimotherapy. This work shoiuld allow 1) a better understanding of mechanisms explaining why some anticancer agents may become inactive, 2) to optimize utilisation of these agents in relationship with MDR-1 gene expression and the B vitamin status, 3) to evaluate impacts of nutritionnal factors (cobalamine) in MDR-1 gene expression and 4) probably developp possible ways to improve chemotherapy
Document type :
Theses
Complete list of metadata

https://hal.univ-lorraine.fr/tel-01749650
Contributor : Thèses Ul <>
Submitted on : Thursday, March 29, 2018 - 12:22:12 PM
Last modification on : Tuesday, October 13, 2020 - 10:46:38 AM
Long-term archiving on: : Friday, September 14, 2018 - 8:11:09 AM

File

DDOC_T_2012_0305_GKIKOPOULOU.p...
Files produced by the author(s)

Identifiers

  • HAL Id : tel-01749650, version 1

Citation

Effrosyni Gkikopoulou. Voies de signalisation cobalamine-dépendantes de l'expression du gène MDR-1. Une cible pharmacologique nouvelle pour la chimiothérapie ?. Médecine humaine et pathologie. Université de Lorraine, 2012. Français. ⟨NNT : 2012LORR0305⟩. ⟨tel-01749650⟩

Share

Metrics

Record views

572

Files downloads

391