Accumulating evidence suggests that overproduction of prostaglandin (PG) E2 attributable to induction of cyclooxygenase-2 plays an important role in the development of lung adenocarcinoma. Recently, we have reported that a PGE2 receptor, EP3 is involved in appearance of malignant phenotype of a lung adenocarcinoma cell (A549 cell). In line with our previous study, here we investigated if Src signaling could be involved in PGE2-stimulated growth of A549 cells via EP3. PGE2-dependent cell growth in A549 cell positively related to the activation of Src. A specific antagonist against EP3 abrogated the cell growth and Src activation in the cells stimulated with PGE2. Also, the inhibition of Src activity suppressed its downstream signaling related to cell growth as well as the cell growth in the cells treated with PGE2. These results indicate that PGE2-dependent activation of Src signaling via EP3 plays an important role in growth of A549 cells. (C) 2004 Elsevier Ireland Ltd. All rights reserved.