NF-kappaB transcription factor induces drug resistance through MDR1 expression in cancer cells.
Oncogene
; 22(1): 90-7, 2003 Jan 09.
Article
em En
| MEDLINE
| ID: mdl-12527911
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
NF-kappa B
/
Neoplasias do Colo
/
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
/
Resistencia a Medicamentos Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Bélgica