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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

A lowered 26S proteasome activity correlates with mantle lymphoma cell lines resistance to genotoxic stress

Authors: Khaoula Ben Younes, Simon Body, Élodie Costé, Pierre-Julien Viailly, Hadjer Miloudi, Clémence Coudre, Fabrice Jardin, Fatma Ben Aissa-Fennira, Brigitte Sola

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

Mantle cell lymphoma (MCL) is a B-cell hemopathy characterized by the t(11;14) translocation and the aberrant overexpression of cyclin D1. This results in an unrestrained cell proliferation. Other genetic alterations are common in MCL cells such as SOX11 expression, mutations of ATM and/or TP53 genes, activation of the NF-κB signaling pathway and NOTCH receptors. These alterations lead to the deregulation of the apoptotic machinery and resistance to drugs. We observed that among a panel of MCL cell lines, REC1 cells were resistant towards genotoxic stress. We studied the molecular basis of this resistance.

Methods

We analyzed the cell response regarding apoptosis, senescence, cell cycle arrest, DNA damage response and finally the 26S proteasome activity following a genotoxic treatment that causes double strand DNA breaks.

Results

MCL cell lines displayed various sensitivity/resistance towards genotoxic stress and, in particular, REC1 cells did not enter apoptosis or senescence after an etoposide treatment. Moreover, the G2/M cell cycle checkpoint was deficient in REC1 cells. We observed that three main actors of apoptosis, senescence and cell cycle regulation (cyclin D1, MCL1 and CDC25A) failed to be degraded by the proteasome machinery in REC1 cells. We ruled out a default of the βTrCP E3-ubiquitine ligase but detected a lowered 26S proteasome activity in REC1 cells compared to other cell lines.

Conclusion

The resistance of MCL cells to genotoxic stress correlates with a low 26S proteasome activity. This could represent a relevant biomarker for a subtype of MCL patients with a poor response to therapies and a high risk of relapse.
Appendix
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Metadata
Title
A lowered 26S proteasome activity correlates with mantle lymphoma cell lines resistance to genotoxic stress
Authors
Khaoula Ben Younes
Simon Body
Élodie Costé
Pierre-Julien Viailly
Hadjer Miloudi
Clémence Coudre
Fabrice Jardin
Fatma Ben Aissa-Fennira
Brigitte Sola
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3530-z

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