Nuclear localization of glutamate-cysteine ligase is associated with proliferation in head and neck squamous cell carcinoma
| Autor: | Isabelle Bar, Dany Brohée, Vincent Nuyens, Luc Vanhamm, Pierrick Uzureau, Didier Dequanter, Philippe Lothaire, Karim Zouaoui Boudjeltia, Paul Delrée, Michel Vanhaeverbeek, Nathalie Nagy, Alexandre Rousseau, Maureen Van de Velde |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Cell In situ hybridization Biology head and neck squamous cell carcinoma 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine oxidative stress glutathione Ki-67 antigen Oncogene GCLM Cell growth Articles Glutathione Cell cycle medicine.disease Molecular biology Head and neck squamous-cell carcinoma Cancérologie 030104 developmental biology medicine.anatomical_structure Oncology chemistry 030220 oncology & carcinogenesis glutamate-cysteine ligase |
| Zdroj: | Oncology Letters, 11 (6 Oncology Letters |
| ISSN: | 1792-1082 1792-1074 |
| Popis: | 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. SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|