Molecular cytogenetic characterization of doxorubicin-resistant neuroblastoma cell lines: evidence that acquired multidrug resistance results from a unique large amplification of the 7q21 region.

Détails

ID Serval
serval:BIB_613AE9F0AC33
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Molecular cytogenetic characterization of doxorubicin-resistant neuroblastoma cell lines: evidence that acquired multidrug resistance results from a unique large amplification of the 7q21 region.
Périodique
Genes, chromosomes & cancer
Auteur(s)
Flahaut M, Mühlethaler-Mottet A, Martinet D, Fattet S, Bourloud KB, Auderset K, Meier R, Schmutz NB, Delattre O, Joseph JM, Gross N
Statut éditorial
Publié
Date de publication
05/2006
Peer-reviewed
Oui
Langue
anglais
Résumé
Neuroblastoma is a heterogeneous neural crest–derived embryonic childhood neoplasm that is the second most common solid tumor found in children. Despite recent advances in combined therapy, the overall survival of patients with high‐stage disease has not improved in the last decades. Treatment failure is in part attributed to multidrug resistance. To address the mechanisms involved in the development of multidrug resistance, we have generated two doxorubicin‐resistant neuroblastoma cell lines (IGRN‐91R and LAN‐1R). These cells were shown to overexpress the MDR1 gene coding for the P‐glycoprotein and were resistant to other MDR1‐ and non‐MDR1‐substrate drugs. Indeed, the MDR1 inhibitor verapamil only partially restored sensitivity to drugs, confirming that P‐glycoprotein‐mediated drug efflux was not responsible for 100% resistance. High‐resolution and array‐based comparative genomic hybridization analyses revealed the presence of an amplicon in the 7q21 region as the unique genomic alteration common to both doxorubicin‐resistant cell lines. In addition to the MDR1 locus, this large amplified region is likely to harbor additional genes potentially involved in the development of drug resistance. This study represents the first molecular cytogenetic and genomic approach to identifying genomic regions involved in the multidrug‐resistant phenotype of neuroblastoma. These results could lead to the identification of relevant target genes for the development of new therapeutic modalities.
Pubmed
Création de la notice
23/03/2020 12:44
Dernière modification de la notice
24/03/2020 7:26
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