Growth factor-like effects of placental alkaline phosphatase in human fetus and mouse embryo fibroblasts

Human placental alkaline phosphatase (PALP) is synthesized in the placenta during pregnancy and is also expressed in many cancer patients; however, it s physiological role is unknown. Here we show that in human fetus fibroblas ts as well as normal and H-ras-transformed mouse embryo fibroblasts PALP st imulates DNA synthesis and cell proliferation in synergism with insulin, zi nc and calcium. The mitogenic effects of PALP are associated with the activ ation of c-Raf-1, p42/p44 mitogen-activated protein kinases, p70 S6 kinase, Akt/PKB kinase and phosphatidylinositol 3'-kinase. The results suggest tha t in vivo PALP may promote fetus development as well as the growth of cance r cells which express oncogenic Ras. (C) 2000 Federation of European Bioche mical Societies.