Metabolites of arachadonic acid participate in normal growth responses and in aberrant cellular growth and proliferation, including carcinogenesis [1, 2]. The key step in the conversion of free arachidonic acid to prostaglandins is catalyzed by the cyclooxygenase enzyme (COX). Until recently, only one isoform of the COX enzyme (COX-1) had been purified and cloned. However, it is now known that a second inducible isoform of the COX enzyme (COX-2) exists. The COX-1 enzyme is constitutively expressed at low levels in a majority of tissues and presumably makes prostaglandins for normal physiological functions. By contrast, COX-2 is not normally present in most cells, but tight regulation allows it to be rapidly expressed in response to growth-related signals resulting in increased prostaglandin synthesis associated with inflammation and carcinogenesis.

Insight into the molecular regulation of COX-2 expression preceded its discovery. Work in the late 1980s identified an inducible COX activity that was temporally regulated on both transcriptional and post-transcriptional levels [3]. Near the same time, at least two independent groups had identified and cloned COX-2 as an immediate-early response gene whose expression was highly induced in response to cellular transformation by v-src [4] or treatment of cells with phorbol ester [5]. Subsequent work led to the cloning of the human COX-2 cDNA from vascular endothelial cells [6, 7] and isolation of the COX-2 gene [8]. Examination of the COX-2 5 promoter region has identified several transcription factor regulatory elements. A number of mRNA instability elements are contained within the 3 untranslated region (3UTR) of COX-2