Nuclear localization of glutamate-cysteine ligase is associated with proliferation in head and neck squamous cell carcinoma

Dequanter,Didier; Van de Velde,Maureen; Bar,Isabelle; Nuyens,Vincent; Rousseau,Alexandre; Nagy,Nathalie; Vanhamm,Luc; Vanhaeverbeek,Michel; Brohée,Dany; Delrée,Paul; Zouaoui Boudjeltia,Karim; Lothaire,Philippe; Uzureau,Pierrick

doi:10.3892/ol.2016.4458

Nuclear localization of glutamate-cysteine ligase is associated with proliferation in head and neck squamous cell carcinoma

Authors:
- Didier Dequanter
- Maureen Van de Velde
- Isabelle Bar
- Vincent Nuyens
- Alexandre Rousseau
- Nathalie Nagy
- Luc Vanhamm
- Michel Vanhaeverbeek
- Dany Brohée
- Paul Delrée
- Karim Zouaoui Boudjeltia
- Philippe Lothaire
- Pierrick Uzureau
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Affiliations: Department of Surgery, University Hospital Center of Charleroi, André Vésale Hospital, Université Libre de Bruxelles, Montigny‑le‑Tilleul B‑611, Belgium, Interdisciplinary Cluster for Applied Genoproteomics, University of Liège, Liège B‑4000, Belgium, Department of Pathology, Institute of Pathology and Genetics, Gosselies B‑6041, Belgium, Laboratory of Experimental Medicine (ULB222), André Vésale Hospital, Université Libre de Bruxelles, Montigny‑le‑Tilleul B‑6110, Belgium , Department of Pathological Anatomy, University Hospital Center in Charleroi, André Vésale Hospital, Université Libre de Bruxelles, Montigny‑le‑Tilleul B‑6110, Belgium, Laboratory of Molecular Parasitology, Institute of Molecular Biology and Medicine, Université Libre de Bruxelles, Charleroi B‑6041, Belgium, Department of Internal Medicine, University Hospital Center in Charleroi, André Vésale Hospital, Université Libre de Bruxelles, Montigny‑le‑Tilleul B‑6110, Belgium, Department of Oncology, University Hospital Center in Charleroi, André Vésale Hospital, Université Libre de Bruxelles, Montigny‑le‑Tilleul B‑6110, Belgium
Published online on: April 19, 2016 https://doi.org/10.3892/ol.2016.4458
Pages: 3660-3668
Copyright: © Dequanter et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glutathione (GSH) is the keystone of the cellular response toward oxidative stress. Elevated GSH content correlates with increased resistance to chemotherapy and radiotherapy of head and neck (HN) tumors. The purpose of the present cross‑sectional study was to evaluate whether the expression of glutamate‑cysteine ligase (GCL) accounts for the increased GSH availability observed in HN squamous cell carcinoma (SCC). For that purpose, the messenger (m)RNA levels of the modifier (M) and catalytic (C) subunits of GCL and its putative regulators (namely, nuclear factor erythroid 2‑related factor 2, heme oxygenase‑1 and nuclear factor of kappa light polypeptide gene enhancer in B‑cells inhibitor, alpha) were monitored in 35 surgical resections of untreated HNSCC. The localization of GCLM was evaluated using in situ hybridization and immunohistochemistry. GCLM expression was significantly increased in tumor samples, compared with normal mucosa, both at the mRNA and protein level (P=0.029), but the pathway of GCLM activation remains to be elucidated. Protein expression of GCLM was detected in the cytoplasm and nucleus. GCLM and the proliferation marker Ki‑67 displayed a similar distribution, being both mainly expressed at the periphery of tumor lobules. The present study reported increased expression of GCL and the rate‑limiting enzyme of GSH synthesis, within HNSCC. The nuclear localization of GCLM and the concomitant expression of Ki‑67 suggested that the localization of GSH synthesis contributes to the protection against oxidative stress within hotspots of cell proliferation.

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