Role of Ets2 in cyclic AMP regulation of the human chorionic gonadotropin β promoter

Activation of the human chorionic gonadotropin beta (hCG beta) by the protein kinase A (PKA) pathway has been shown to occur through an activating protein-2 (AP-2)-dependent mechanism. However, in HepG2 cells, which are deficient in AP-2, the PKA catalytic subunit is still able to stimulate the hCG beta promoter. Ets2 plays a critical role in placental development as revealed by placental abnormalities in Ets2 knockout mice. Transfection of Ets2 into JEG-3 placental cells causes a slight, but reproducible, increase in hCG beta promoter basal activity. However, cotransfection with the PKA catalytic subunit causes a strong synergistic increase in hCG beta promoter activity. Ets2 synergistic activation of the hCG beta promoter is specific for the PKA pathway, as activation of the ras pathway, which also acts through Ets2, does not activate the hCG beta promoter, c-Jun-mediated repression of hCG beta is inhibited by Ets' cotransfection, indicating that protein-protein interactions may be responsible for Ets2 activation of the hCG beta promoter. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.