Alteration of APE1/ref-1 expression in non-small cell lung cancer: the implications of impaired extracellular superoxide dismutase and catalase antioxidant systems.
Lung Cancer
; 60(2): 277-84, 2008 May.
Article
em En
| MEDLINE
| ID: mdl-18061304
ABSTRACT
PURPOSE:
Apurinic/apyrimidinic endonuclease1/ref-1(APE1/ref-1) is a key enzyme in the base excision repair and in transcriptional modulation against oxidative stress. We investigated the altered expression of APE1/ref-1 and antioxidant systems in lung cancer. PATIENTS ANDMETHODS:
Tumor specimens from 48 patients with operable non-small cell lung cancer were obtained from 2004 to 2006. Immunohistochemistry, Western blot, lipid peroxidation and superoxide production were performed on the tumor samples and a cultured H460 cell line.RESULTS:
APE1/ref-1 was mainly localized to the nucleus in the non-tumor regions of the lung cancer tissue specimens. However, nuclear and cytoplasmic expressions of APE1/ref-1 in the lung cancers were markedly up-regulated in the non-small cell lung cancer (NSCLC) specimens including squamous cell and adenocarcinoma specimens. Extracellular superoxide dismutase (ECSOD) and catalase were down-regulated and manganese superoxide dismutase (MnSOD) was up-regulated in the tumor regions of the NSCLC. Tumor regions of the NSCLC showed higher superoxide production and lipid peroxidation levels than non-tumor regions. In the lung adenocarcinoma cell line, H460, treatment with hydrogen peroxide in the presence of a catalase inhibitor, aminotriazole, increased APE1/ref-1 expression, suggesting oxidative stress might have contributed to the induction of APE1/ref-1.CONCLUSION:
The results of this study suggest that APE1/ref-1 is up-regulated in the tumor regions of NSCLC. Altered expression of antioxidant systems lead to enhanced production of superoxide production and lipid peroxidation, which can induce APE1/ref-1 in the tumor regions of NSCLS.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
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Líquido Extracelular
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DNA Liase (Sítios Apurínicos ou Apirimidínicos)
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Neoplasias Pulmonares
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Antioxidantes
Limite:
Aged
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article