Mechanisms by which PGE
interacts with EGFR-mediated signalling in hepatocytes and MH
hepatocarcinoma cells. A) In normal rat hepatocytes, PGE2 does not elicit transactivation of EGFR, but induces upregulation of the effectiveness in Ras/ERK and PI3K/Akt pathways downstream of EGFR, leading to an enhanced mitogenic response to EGF family growth factors [37, 38, 51]. Although not fully clarified, previous studies have indicated that this effect of PGE2 is mediated primarily through EP3 receptors and Gi proteins, requires several hours to develop, and is most likely a result of altered gene expression [34, 37, 38, 51, 52]. B) In MH1C1 rat hepatocarcinoma cells, PGE2 transactivates EGFR and thereby activates the Ras/ERK and PI3K/Akt signalling pathways. The results of the present study suggest that this effect is exerted via FP receptors, Gq proteins, PLCβ, intracellular Ca2+ (but not PKC), Src, and ADAM-mediated release of EGFR ligands.