title: Is galectin-1 a trigger for trophoblast cell fusion?: the MAP-kinase pathway and syncytium formation in trophoblast tumour cells BeWo.
abstract: Galectin-1 (gal-1), a member of the mammalian β-galactoside-binding proteins, exerts biological effects by recognition of glycan ligands, including those involved in cell adhesion and growth regulation. In a previous study, we demonstrated that gal-1 induces cell differentiation processes on the membrane of choriocarcinoma cells BeWo, including the receptor tyrosine kinases, REarranged during transfection, janus kinase 2 and vascular endothelial growth factor receptor 3. Within this study, we examined which mitogen-activated protein kinases (MAPK) and serine/threonine kinases were phoshorylated by gal-1. Out of a number of 21 different MAPKs and other serine/threonine kinases, the stimulation of BeWo cells with gal-1 showed a significant alteration of signal intensity in extracellular-regulated kinases 1/2 (ERK1/2), Akt-3, Akt-pan and glycogen synthase kinase-α/β (GSK-3α/β). We demonstrated that gal-1 significantly inhibited ERK1/2, Akt-3/pan and GSK-3α/β phosphorylation in BeWo cells and in addition induced Elk1 transcription factor activation. In contrast to gal-1 effects, MAPK inhibitor U0126 reduced syncytium formation of BeWo cells. The results of our data showed that phosphorylation of MAP kinases are involved in gal-1-induced signal transduction processes in BeWo cells. Additional results obtained with MAPK inhibitor U0126 close the gap between syncytium formation induced by gal-1 and MAPK activation in trophoblast cells. Furthermore, we demonstrated that gal-1 induces the activation of Elk1, a transcription factor that is activated by MAPK pathways.
authors.affiliation: Department of Obstetrics and Gynecology,  Ludwig Maximilians University of Munich, Maistrasse 11, 80337 Munich,  Germany.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fischer
authors.forename: Maja
authors.initials: M
authors.lastname: Weber
authors.forename: Christina
authors.initials: C
authors.lastname: Kuhn
authors.forename: Justine S
authors.initials: JS
authors.lastname: Fitzgerald
authors.forename: Sandra
authors.initials: S
authors.lastname: Schulze
authors.forename: Klaus
authors.initials: K
authors.lastname: Friese
authors.forename: Hermann
authors.initials: H
authors.lastname: Walzel
authors.forename: Udo R
authors.initials: UR
authors.lastname: Markert
authors.forename: Udo
authors.initials: U
authors.lastname: Jeschke
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002459:Cell Fusion; D002822:Choriocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D037483:Galectin 1 / Q000378:metabolism / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015726:Giant Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050807:ets-Domain Protein Elk-1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D037483:Galectin 1; D009570:Nitriles; C113580:U 0126; D050807:ets-Domain Protein Elk-1; D053614:Janus Kinase 2; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha