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

Abstract

Human placental alkaline phosphatase (PALP) is synthesized in the placenta during pregnancy and is also expressed in many cancer patients; however, its physiological role is unknown. Here we show that in human fetus fibroblasts as well as normal and H-ras-transformed mouse embryo fibroblasts PALP stimulates DNA synthesis and cell proliferation in synergism with insulin, zinc and calcium. The mitogenic effects of PALP are associated with the activation of c-Raf-1, p42/p44 mitogen-activated protein kinases, p70 S6 kinase, Akt/PKB kinase and phosphatidylinositol 3P P-kinase. The results suggest that in vivo PALP may promote fetus development as well as the growth of cancer cells which express oncogenic Ras.z 2000 Federation of European Biochemical Societies.

Crystal Structure of Alkaline Phosphatase from Human Placenta at 1.8 Å Resolution

“…This loop interacts with and may be stabilized by the putative calcium ion. It could therefore be responsible for the synergism observed between calcium and PLAP activity by intervening in substrate binding (15). In summary, the organization of the extended active site would be consistent with PLAP interacting with a large substrate.…”

“…In NSAP, this specificity involves binding to collagen (11,12). In PLAP, evidence has accumulated over the past few years suggesting a role in cell division in both normal and transformed cells (13)(14)(15)(16). This role probably occurs through its phosphatase activity against phosphorylated proteins (14,17).…”

Diagnostic Utility of Heat Stable Alkaline Phosphatase in Hypertensive Disorders of Pregnancy

“…Our study also shows that there is a good positive correlation between PLAP and blood pressure. Alkaline phosphatase is a ubiquitous enzyme involved in the transport of sugar and phosphate across the trophoblast cell membranes [22]. In normal pregnancy, the serum level of Total ALP is raised, attributable to the placental isoenzyme.…”

“…Decreased serum PLAP in pregnant women could be associated with intrauterine growth retardation (IUGR), premature rupture of membranes and premature labour [25]. It has been observed that in human fetal fibroblasts, PLAP stimulates DNA synthesis and cell proliferation in synergism with insulin, Zinc and Calcium, thus playing an important role in promoting fetal development [22].…”

Inhibition of cell transformation by resveratrol and its derivatives: differential effects and mechanisms involved

“…The cells were treated for the indicated times with different concentrations of resveratrol, its derivatives or their vehicle, DMSO (o0.1%), which was used as a negative control. The relative changes in the number of viable cells were determined by the MTT assay as described previously (She et al, 2000), and a Labsystem Multiskan MS microplate reader was used to read the absorbance of formazan at a wavelength of 540 nm (She et al, 2000).…”