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The Effect of Uteroglobin on cPLA2, COX-2 Expression and ERK Activation in NSCLC Cells

Tuberculosis & Respiratory Diseases / Tuberculosis & Respiratory Diseases,
2004, v.56 no.6, pp.638-645








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Abstract

Background:Uteroglobin is a protein produced by the normal bronchial epithelium and its expression level is lower in non-small cell lung cancer tissues and cell lines. It mainly functions as an anti-inflammatory, and when it is overexpressed in cancer cells, the neoplastic phenotype is antagonized. cPLA2 and COX-2, which are also associated with inflammation, were reported to be related to cancer. The relationship between cPLA2, COX-2 and uteroglobin is unclear. The relationship between uteroglobin and ERK, which is related to cell growth, is also not unclear. This study investigated the changes in the cPLA2 and COX-2 expression levels and the ERK activities after the overexpression of uteroglobin in non-small cell lung cancer cell lines.Methods:The A549 and NCI-H460 cell lines were infected by adenovirus-null and adenovirus- uteroglobin. The cChange in the cPLA2, COX-2 expression level and ERK activity after uteroglobin overexpression was measured by Western blot. The change in MMP activity was measured by zymography.Results:Western blot revealed decreased expression levels of cPLA2, and COX-2, and increased pERK levels in nonsmall cell lung cancer cells after uteroglobin overexpression. Zymography revealed no changes in the MMP-2 activity and lower MMP-9 activity. U0126, which is a specific inhibitor of ERK-activating kinase MEK-1/-2, prevented the decrease in the MMP-9 activityConclusions: A decrease in cPLA2 expression, COX-2 expression, MMP-9 activity and a increase in ERK activity may be related to the anticancer effects of uteroglobin in nonsmall cell lung cancer cells.(Tuberculosis and Respiratory Diseases 2004, 56:638-645)

keywords
Uteroglobin, Lung cancer, cPLA2, COX-2, ERK.

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Tuberculosis & Respiratory Diseases