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Increased frequency of aberrations in the p53/MDM2/p14ARF pathway in neuroblastoma cell lines established at relapse

Carr-Wilkinson, Jane, Bell, Emma, Pearson, Andrew D. J., Kees, Ursula, Beris, Helen, Lunec, John and Tweddle, Deborah A. (2006) Increased frequency of aberrations in the p53/MDM2/p14ARF pathway in neuroblastoma cell lines established at relapse. The Journal of Cancer Research, 66 (4). pp. 2138-2145.

Item Type: Article

Abstract

p53 mutations have been reported in cell lines derived from relapsed neuroblastoma tumors. We hypothesize that functional inactivation of p53 by mutation or other mechanisms is common in relapsed neuroblastoma and can contribute to chemoresistance. Our aim was to determine the frequency of p53 mutations, p14ARF methylation, or deletion and MDM2 amplification in 23 neuroblastoma cell lines (6 derived at diagnosis and 17 derived at relapse). One cell line was p53 mutant (BE2c) and two cell lines were deleted for p14ARF (LAN-6 and SHEP). Two cell lines were methylated for p14ARF (GIMEN and PER-108), one of which had low levels of p14ARF mRNA expression which increased following demethylation with 5-aza-2/deoxycytidine treatment (GIMEN), and four cell lines were confirmed to be MDM2-amplified. All these cell lines were derived from neuroblastomas at relapse. Inactivation of the p53 pathway was observed in 9 out of 17 neuroblastoma cell lines (53%) established at relapse and in none of the cell lines established from pretreatment tumors. If these data are confirmed in neuroblastoma tumors, this suggests that p53-independent therapy and reactivation of inactive p53 approaches would be useful in the management of relapsed neuroblastoma. (Cancer Res 2006; 66(4): 2138-45)

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More Information

Depositing User: Paula Normington

Identifiers

Item ID: 5890
Identification Number: https://doi.org/10.1158/0008-5472.CAN-05-2623
URI: http://sure.sunderland.ac.uk/id/eprint/5890

Users with ORCIDS

Catalogue record

Date Deposited: 22 Jan 2016 11:05
Last Modified: 18 Dec 2019 15:38

Contributors

Author: Jane Carr-Wilkinson
Author: Emma Bell
Author: Andrew D. J. Pearson
Author: Ursula Kees
Author: Helen Beris
Author: John Lunec
Author: Deborah A. Tweddle

University Divisions

Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences
Faculty of Health Sciences and Wellbeing > School of Nursing and Health Sciences

Subjects

Sciences

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