PT - JOURNAL ARTICLE AU - MIRAL R. SADARIA AU - JESSICA A. YU AU - XIANZHONG MENG AU - DAVID A. FULLERTON AU - T. BRETT REECE AU - MICHAEL J. WEYANT TI - Secretory Phospholipase A<sub>2</sub> Mediates Human Esophageal Adenocarcinoma Cell Growth and Proliferation <em>via</em> ERK 1/2 Pathway DP - 2013 Apr 01 TA - Anticancer Research PG - 1337--1342 VI - 33 IP - 4 4099 - http://ar.iiarjournals.org/content/33/4/1337.short 4100 - http://ar.iiarjournals.org/content/33/4/1337.full SO - Anticancer Res2013 Apr 01; 33 AB - Background/Aim: Secretory phospholipase-A2 (sPLA2) mediates growth and proliferation of human esophageal adenocarcinoma cells (HEAC). Two major molecular pathways of cancer growth regulation include extracellular signal-regulated kinase 1/2 (ERK 1/2) and protein kinase-B (AKT). Phospholipase enzymes have been demonstrated to significantly influence these two growth regulating pathways in other tumor cells. We hypothesize sPLA2 to mediate HEAC growth control through ERK 1/2 and AKT. Materials and Methods: Verified HEAC (FLO-1), treated with either the mitogen-activated protein kinase kinase selective inhibitor (PD98059) or with group IIa sPLA2-specific inhibitor, were assessed for ERK1/2 phosphorylation and AKT activation after tumor necrosis factor-alpha stimulation, as well as for viability, proliferation, and apoptosis responses. Results: PD98059 significantly inhibited ERK 1/2 activation, reduced cell viability, and reduced proliferation (p&lt;0.05). sPLA2 inhibition attenuated ERK 1/2 activation (p&lt;0.01) but had no effect on AKT activation or apoptosis. Conclusion: Specific inhibition of group IIa sPLA2 directly reduces HEAC viability and proliferation by attenuating ERK 1/2 activation with no effect on AKT activation or apoptosis. This may indicate that the mechanism of action of sPLA2 is mainly the induction of growth arrest.