Epidermal growth factor coordinately regulates the expression of prostaglandin G/H synthase and cytosolic phospholipase A2 genes in embryonic mouse cells.

Confluent, primary cultures of mouse embryo palate mesenchyme (MEPM) cells are refractory to activation of phospholipase A2 (PLA2) by the calcium ionophore A23187. However, treatment of these cultures with epidermal growth factor (EGF) permits the cells to activate PLA2 in response to A23187. We have developed this finding by exploring molecular mechanisms by which growth factors modulate mobilization and metabolism of arachidonic acid. We found chronic treatment (> 6 h) of confluent MEPM cells with EGF (a) increases their ability to metabolize exogenous arachidonic acid to prostaglandin E2 (PGE2) and (b) stimulated constitutive expression of activities of PLA2 and cyclooxygenase (CyOx). Immunoprecipitation of [35S]proteins and Western blot analysis revealed EGF treatment stimulated synthesis and accumulation of PLA2c, CyOx-1, and CyOx-2. Northern hybridization analysis revealed EGF increased the steady-state levels of a transcript for the high molecular weight, cytosolic PLA2 (PLA2c), and both the 2.8- and 4.2-kb transcripts for CyOx-1 and CyOx-2, respectively. In vitro nuclear transcription assays showed a parallel increase in the transcription rate of the genes corresponding to CyOx-1 and PLA2c, but not CyOx-2, in response to EGF. Treatment with EGF had no effect on either synthesis of the low molecular weight, group II PLA2, accumulation of its transcript, or the transcription rate of its gene. Coordinate regulation of activities of PLA2 and CyOx in response to EGF did not parallel the mitogenic effects of EGF on confluent MEPM cells.