1.Nuclear factor E2-related factor 2 Dependent Overexpression of Sulfiredoxin and Peroxiredoxin III in Human Lung Cancer.
Young Sun KIM ; Hye Lim LEE ; Ki Bum LEE ; Joo Hun PARK ; Wou Young CHUNG ; Keu Sung LEE ; Seung Soo SHEEN ; Kwang Joo PARK ; Sung Chul HWANG
The Korean Journal of Internal Medicine 2011;26(3):304-313
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.
Adenocarcinoma/*enzymology/genetics/mortality/pathology
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Animals
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Antineoplastic Agents, Phytogenic/pharmacology
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Blotting, Western
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Camptothecin/pharmacology
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Carcinoma, Squamous Cell/*enzymology/genetics/mortality/pathology
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Cell Line, Tumor
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Humans
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Immunohistochemistry
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Lung Neoplasms/*enzymology/genetics/mortality/pathology
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Mink
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NF-E2-Related Factor 2/*metabolism
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Oxidoreductases Acting on Sulfur Group Donors/genetics/*metabolism
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Peroxiredoxin III/*metabolism
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Peroxiredoxins/metabolism
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Prognosis
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RNA Interference
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Reactive Oxygen Species/metabolism
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Transfection
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Transforming Growth Factor beta1/metabolism
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Tumor Necrosis Factor-alpha/metabolism
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Up-Regulation
2.Role of tissue inhibitors of metalloproteinases (TIMPs) in colorectal carcinoma.
Young Eun JOO ; Kang Seok SEO ; Jin KIM ; Hyun Soo KIM ; Jong Sun REW ; Chang Soo PARK ; Sei Jong KIM
Journal of Korean Medical Science 1999;14(4):417-423
Increased production of matrix metalloproteinases (MMPs) has been associated with increases in invasive and metastatic potential in many types of human carcinoma. Tissue inhibitors of metalloproteinase (TIMP)-1 inhibits most interstitial collagenases and MMP-9. TIMP-2 binds specifically and noncovalently to the pro-form of MMP-2 and inhibits its enzyme activity. In this study, we examined TIMP-1 and TIMP-2 expressions in relation to clinicopathological variables in colorectal carcinoma with in situ hybridization and immunohistochemistry. TIMP-1 and TIMP-2 expressions were localized overwhelmingly to pericancer stromal cells, while malignant and normal mucosal cells were weak or negative. Strong stromal TIMP-1 immunoreactivity correlated with Dukes' stage (p=0.022), status of lymph node metastasis (p=0.044) and poor survival (p= 0.005). The degree of immunohistochemical staining of TIMP-2 did not correlate with all clinicopathological variables. The correlation between enhanced TIMP-1 expression and advanced stage and poor survival suggest a growth promoting activity of TIMP-1 in colorectal carcinoma.
Adenocarcinoma/pathology
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Adenocarcinoma/mortality
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Adenocarcinoma/enzymology*
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Adult
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Aged
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Aged, 80 and over
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Antibodies
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Collagenases/immunology
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Collagenases/genetics*
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Collagenases/analysis
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Colorectal Neoplasms/pathology
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Colorectal Neoplasms/mortality
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Colorectal Neoplasms/enzymology*
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DNA Probes
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Female
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Gelatinase A
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Gelatinase B
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Gelatinases/immunology
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Gelatinases/genetics*
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Gelatinases/analysis
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Gene Expression Regulation, Enzymologic
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Gene Expression Regulation, Neoplastic
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Human
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In Situ Hybridization
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Male
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Metalloendopeptidases/immunology
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Metalloendopeptidases/genetics*
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Metalloendopeptidases/analysis
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Middle Age
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Predictive Value of Tests
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RNA, Messenger/analysis
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Stromal Cells/pathology
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Stromal Cells/enzymology
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Survival Analysis
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Tissue Inhibitor-of Metalloproteinase-2/immunology
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Tissue Inhibitor-of Metalloproteinase-2/genetics*
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Tissue Inhibitor-of Metalloproteinase-2/analysis
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Tissue-Inhibitor of Metalloproteinase-1/immunology
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Tissue-Inhibitor of Metalloproteinase-1/genetics*
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Tissue-Inhibitor of Metalloproteinase-1/analysis