Korean J Intern Med.  2011 Sep;26(3):304-313. 10.3904/kjim.2011.26.3.304.

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

• Kim YS
• Lee HL
• Lee KB
• Park JH
• Chung WY
• Lee KS
• Sheen SS
• Park KJ
• Hwang SC

• KMID: 1022170
• DOI: http://doi.org/10.3904/kjim.2011.26.3.304

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-beta1, tumor necrosis factor-alpha, 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.

Keyword

GA-binding protein transcription factor; Peroxiredoxins; Sulfiredoxin; Lung neoplasms

MeSH Terms

Adenocarcinoma/*enzymology/genetics/mortality/pathology
Animals
Antineoplastic Agents, Phytogenic/pharmacology
Blotting, Western
Camptothecin/pharmacology
Carcinoma, Squamous Cell/*enzymology/genetics/mortality/pathology
Cell Line, Tumor
Humans
Immunohistochemistry
Lung Neoplasms/*enzymology/genetics/mortality/pathology
Mink
NF-E2-Related Factor 2/*metabolism
Oxidoreductases Acting on Sulfur Group Donors/genetics/*metabolism
Peroxiredoxin III/*metabolism
Peroxiredoxins/metabolism
Prognosis
RNA Interference
Reactive Oxygen Species/metabolism
Transfection
Transforming Growth Factor beta1/metabolism
Tumor Necrosis Factor-alpha/metabolism
Up-Regulation