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Nuclear factor E2-related factor 2 Dependent Overexpression of Sulfiredoxin and Peroxiredoxin III in Human Lung Cancer

Authors
Kim, YS; Lee, HL; Lee, KB; Park, JH; Chung, WY; Lee, KS; Sheen, SS; Park, KJ; Hwang, SC
Citation
The Korean journal of internal medicine, 26(3):304-313, 2011
Journal Title
The Korean journal of internal medicine
ISSN
1226-33032005-6648
Abstract
Background/Aims: Oxidative stress results in protein oxidation and is implicated in carcinogenesis. Sulfiredoxin (Srx) is responsible for the enzymatic reversal of inactivated peroxiredoxin (Prx). Nuclear factor E2-related factor 2 (Nrf2) binds to antioxidant responsive elements and upregulates the expression of Srx and Prx during oxidative stress. We aimed to elucidate the biological functions and potential roles of Srx in lung cancer.



Methods: To study the roles of Srx and Prx III in lung cancer, we compared the protein levels of Nrf2, Prxs, thioredoxin, and Srx in 40 surgically resected human lung cancer tissues using immunoblot and immunohistochemical analyses. Transforming growth factor-β1, tumor necrosis factor-α, and camptothecin treatment were used to examine Prx III inactivation in Mv1Lu mink lung epithelial cells and A549 lung cancer cells.



Results: Prx I and Prx III proteins were markedly overexpressed in lung cancer tissues. A significant increase in the oxidized form of a cysteine sulfhydryl at the catalytic site of Prxs was found in carcinogenic lung tissue compared to normal lung tissue. Densitometric analyses of immunoblot data revealed significant Srx expression, which was higher in squamous cell carcinoma tissue (60%, 12/20) than in adenocarcinoma (20%, 4/20). Also, Nrf2 was present in the nuclear compartment of cancer cells.



Conclusions: Srx and Prx III proteins were markedly overexpressed in human squamous cell carcinoma, suggesting that these proteins may play a protective role against oxidative injury and compensate for the high rate of mitochondrial metabolism in lung cancer.
Keywords
GA-binding protein transcription factorPeroxiredoxinsSulfiredoxinLung neoplasms
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
Journal Papers > School of Medicine / Graduate School of Medicine > Medical Science
Journal Papers > School of Medicine / Graduate School of Medicine > Pulmonary & Critical Care Medicine
AJOU Authors
이, 기범박, 주헌정, 우영이, 규성신, 승수박, 광주황, 성철
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