Reference : NF-κB transcription factor induces drug resistance through MDR1 expression in cancer cells
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/3694
NF-κB transcription factor induces drug resistance through MDR1 expression in cancer cells
English
Bentires-Alj, Mohamed [> >]
Barbu, Véronique [> >]
Fillet, Marianne mailto [Université de Liège - ULg > Département de pharmacie > Analyse des médicaments >]
Chariot, Alain mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Relic, Biserka [Centre Hospitalier Universitaire de Liège - CHU > > Rhumatologie >]
Jacobs, Nathalie mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Gielen, Jacques [> >]
Merville, Marie-Paule mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Bours, Vincent mailto [> >]
2003
Oncogene
Nature Publishing Group
22
90-97
Yes (verified by ORBi)
International
0950-9232
1476-5594
Basingstoke
United Kingdom
[en] NF-kappa B ; MDR1 ; cancer
[en] The ubiquitous NF-kappaB transcription factor has been reported to inhibit apoptosis and to induce drug resistance in cancer cells. Drug resistance is the major reason for cancer therapy failure and neoplastic cells often develop multiple mechanisms of drug resistance during tumor progression. We observed that NF-kappaB or P-glycoprotein inhibition in the HCT15 colon cancer cells led to increased apoptotic cell death in response to daunomycin treatment. Interestingly, NF-kappaB inhibition through transfection of a plasmid coding for a mutated IkappaB-alpha inhibitor increased daunomycin cell uptake. Indeed, the inhibition of NF-kappaB reduced mdr1 mRNA and P-glycoprotein expression in HCT15 cells. We identified a consensus NF-kappaB binding site in the first intron of the human mdr1 gene and demonstrated that NF-kappaB complexes could bind with this intronic site. Moreover, NF-kappaB transactivates an mdr1 promoter luciferase construct. Our data thus demonstrate a role for NF-kappaB in the regulation of the mdr1 gene expression in cancer cells and in drug resistance.
Giga-Signal Transduction
FNRS, TELEVIE, ARC ULG, FBC, CAC
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/3694

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