Cytosolic Phospholipase A₂ Is Involved In Epidermal Growth Factor And Fetal Bovine Serum-induced Proliferation In Hela Cells

EGF signaling pathway has been widely investigated. It initiates the EGFR-ras pathway to pass the mitogenic sigal, activates MAPKs to regulate transcription factors(such as c-myc and c-fos), and finally promotes cell grow and proliferation. Moreover ERKl/2 of MAPKs play a crucial role in that process. It should be noticed that cPLA₂, as an important isoform of PLA₂, can be phosphorylated by ERK1/2. It has recently become evident that arachidonic acid (AA), as one of production of PLA₂-mediated hydrolysis of glycerophospholipids, and its metabolites play an important role in cell survival and grow. It indicates the possible relationship between cPLA₂ and cell proliferation. However, the precise mechanism by which cPLA₂ regulates cell proliferation is still uncertain.To explore further the effect of cPLA₂ on cell proliferation process, we used two different mitogens EGF and FBS to induce Hela proliferation, and separately inhibited cPLA₂ activity and expression by AACOCF₃ and cPLA₂ antisense oligonucleotide. At the same time, the changes of Hela cell proliferation and cell cycle were detected. Detailed approaches are as followed:1. First, MEK1/2 specific inhibitor U0126 was used to inhibit ERK1/2, followed by EGF or FBS treatment. Then, cell proliferation, cell cycle and cPLA₂ activity of each group were assayed. The results showed that both EGF and FBS induced Hela proliferation obviously with the similar effects, and increased cPLA₂ activity with a little more effect of EGF. We also observed that U0126 significantly attenuated cell proliferation and cPLA₂ activity in dose-dependent manner, and decreased the percentage of cells in...