Prostaglandin E2 (PGE2) has been implicated as an inducer of angiogenesis in human colon cancer. Here, we demonstrate that PGE2 exposure induces the expression of vascular endothelial growth factor (VEGF) mRNA in HCT116 human colon carcinoma cells that is mediated by the transcriptional activator hypoxia-inducible factor 1 (HIF-1). PGE2 exposure induces the phosphorylation of extracellular signal-regulated kinase (ERK) and AKT. Pharmacologic inhibition of ERK phosphorylation blocks the induction of VEGF mRNA and HIF-1α protein expression in response to PGE2 stimulation. Inhibition of C-SRC tyrosine kinase activity also blocks PGE2-induced HIF-1α protein and VEGF mRNA expression without blocking ERK phosphorylation. In contrast, phosphorylation of AKT is dependent on ERK and C-SRC activity. Thus, the activity of multiple signal transduction pathways is required for the HIF-1-mediated induction of VEGF expression in colon cancer cells exposed to PGE2.
|Original language||English (US)|
|Number of pages||5|
|State||Published - May 1 2003|
ASJC Scopus subject areas
- Cancer Research