Abstract B29: GILZ mediates glucocorticoid action and inhibits hypoxia-induced COX-2 expression in A549 cells

Abstract

Abstract The COX-2/PGE2 pathway in hypoxic cancer cells has important implications for stimulation of inflammation and tumourigenesis. Glucocorticoid receptor (GR) strongly suppresses COX-2 expression induced by inflammatory stimuli. However, the role of GR pathway on COX-2 induction by hypoxia and the mechanisms involved are not known. We examined whether the hypoxia induction of COX-2 was under the influence of glucocorticoid; we found that COX-2 promoter activity and mRNA and protein levels were depressed by dexamethasone and antagonized by the glucocorticoid receptor (GR) antagonist RU486. Overexpression of glucocorticoid-induced leucine zipper (GILZ) inhibited hypoxia-induced COX-2 promoter activity, and knockdown of GILZ by shRNA reduced glucocorticoid inhibition of hypoxia-induced COX-2 expression. Finally, we show that dexamethasone and GILZ inhibits cell invasion by hypoxia in A549 cells. Our results suggest that GR inhibits the hypoxic induction of COX-2 expression via GILZ and regulates cell invasion under hypoxia in A549 cells. Citation Format: WonChung Lim, YoungJoo Lee. GILZ mediates glucocorticoid action and inhibits hypoxia-induced COX-2 expression in A549 cells. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B29. doi:10.1158/1538-7445.CHTME14-B29