Nuclear localization of glutamate-cysteine ligase is associated with proliferation in head and neck squamous cell carcinoma.
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 usingin situhybridization 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.
Department of Surgery, University Hospital Center of Charleroi, André Vésale Hospital, Université Libre de Bruxelles, Montigny-le-Tilleul B-6110, Belgium.
Didier
D
Dequanter
Interdisciplinary Cluster for Applied Genoproteomics, University of Liège, Liège B-4000, Belgium.
Maureen
M
VAN DE Velde
Department of Pathology, Institute of Pathology and Genetics, Gosselies B-6041, Belgium.
Isabelle
I
Bar
Laboratory of Experimental Medicine (ULB222), André Vésale Hospital, Université Libre de Bruxelles, Montigny-le-Tilleul B-6110, Belgium.
Vincent
V
Nuyens
Laboratory of Experimental Medicine (ULB222), André Vésale Hospital, Université Libre de Bruxelles, Montigny-le-Tilleul B-6110, Belgium.
Alexandre
A
Rousseau
Department of Pathological Anatomy, University Hospital Center in Charleroi, André Vésale Hospital, Université Libre de Bruxelles, Montigny-le-Tilleul B-6110, Belgium.
Nathalie
N
Nagy
Laboratory of Molecular Parasitology, Institute of Molecular Biology and Medicine, Université Libre de Bruxelles, Charleroi B-6041, Belgium.
Luc
L
Vanhamme
Department of Internal Medicine, University Hospital Center in Charleroi, André Vésale Hospital, Université Libre de Bruxelles, Montigny-le-Tilleul B-6110, Belgium.
Michel
M
Vanhaeverbeek
Department of Oncology, University Hospital Center in Charleroi, André Vésale Hospital, Université Libre de Bruxelles, Montigny-le-Tilleul B-6110, Belgium.
Dany
D
Brohée
Department of Pathology, Institute of Pathology and Genetics, Gosselies B-6041, Belgium.
Paul
P
Delrée
Laboratory of Experimental Medicine (ULB222), André Vésale Hospital, Université Libre de Bruxelles, Montigny-le-Tilleul B-6110, Belgium.
Karim
K
Boudjeltia
Department of Surgery, University Hospital Center of Charleroi, André Vésale Hospital, Université Libre de Bruxelles, Montigny-le-Tilleul B-6110, Belgium.
Philippe
P
Lothaire
Laboratory of Experimental Medicine (ULB222), André Vésale Hospital, Université Libre de Bruxelles, Montigny-le-Tilleul B-6110, Belgium.
Pierrick
P
Uzureau
Ki-67 antigen; glutamate-cysteine ligase; glutathione; head and neck squamous cell carcinoma; oxidative stress