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

Activation of the human chorionic gonadotropin beta (hCGbeta) 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 hCGbeta 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 hCGbeta promoter basal activity. However, cotransfection with the PKA catalytic subunit causes a strong synergistic increase in hCGbeta promoter activity. Ets2 synergistic activation of the hCGbeta promoter is specific for the PKA pathway, as activation of the ras pathway, which also acts through Ets2, does not activate the hCGbeta promoter. c-Jun-mediated repression of hCGbeta is inhibited by Ets2 cotransfection, indicating that protein-protein interactions may be responsible for Ets2 activation of the hCGbeta promoter.