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

Kim, Woo Jin; Yoon, Jung Min; Lee, Kyoung Hee; Han, Seon Jin; Shin, Won Hyuk; Yim, Jae Joon; Yoo, Chul Gyu; Lee, Choon Taek; Han, Sung Koo; Shim, Young Soo; Kim, Young Whan

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 activity
CONCLUSIONS
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.