However, the precise mechanisms by which COX-2 exerts these effects in tumour cells are unclear. Enhanced COX-2 expression in cells alters susceptibility to tumour necrosis factor-related apoptosis-inducing ligand by reduction in membrane death receptors (Tang et al, 2002) and may also alter the threshold for intrinsic pathway activation (Tang et al, 2002) . Over-expression of COX-2 leads to the generation of prostanoids, particularly PGE 2 , and signalling through the various EP receptors, several of which have been implicated in carcinogenesis (Watanabe et al, 1999; Sonoshita et al, 2001; Mutoh et al, 2002) . PGE 2 stimulates TCF-b-catenin-mediated gene transcription (Castellone et al, 2005; Shao et al, 2005; Eisinger et al, 2007) , possibly by activation of EP2 and EP4 receptors (Fujino et al, 2002) . Some of the important effects of PGE 2 are probably also related to its ability to transactivate the epidermal growth factor receptor through a number of distinct mechanisms (Pai et al, 2002; Shao et al, 2003; Al-Salihi et al, 2007) . It seems likely therefore that prostaglandins generated by CRC cells do not exert their activity by a single mechanism but have a range of downstream signalling targets.