title: Leukaemia inhibitory factor mediated proliferation of HTR-8/SVneo trophoblast cells is dependent on activation of extracellular signal-regulated kinase 1/2.
abstract: Leukaemia inhibitory factor (LIF) is one of the cytokines that is indispensable for embryo implantation. The aim of the present study was to investigate the role of activation of extracellular signal-regulated kinase (ERK) 1/2 in LIF-mediated proliferation of HTR-8/SVneo cells. Stimulation of HTR-8/SVneo cells with LIF (50 ng mL(-1)) resulted in an increase in cell proliferation (P < 0.05) via increased transition of cells to the G(2)/M phase of cell cycle. Stimulation with LIF resulted in the activation of both signal transducer and activator of transcription (STAT) 3 Tyr(705) and ERK1/2, but inhibition of ERK1/2 signalling by pretreatment of cells with U0126 (10 µM) for 2h resulted in abrogation of LIF-mediated increases in G(2)/M transition, with a significant decrease (P < 0.05) in absolute cell numbers compared with control. Although STAT3 silencing had no effect on LIF-dependent proliferation of HTR-8/SVneo cells, it did result in an increase in cell apoptosis, which increased further upon inhibition of ERK1/2 activation irrespective of LIF stimulation. Stimulation of cells with LIF increased the Bcl-2/Bax ratio, whereas ERK1/2 inhibition decreased the Bcl-2/Bax ratio, even after LIF stimulation. Hence, it can be inferred that ERK1/2 activation is essential for LIF-mediated increases in proliferation and that both STAT3 and ERK1/2 activation are important for the survival of HTR-8/SVneo cells.
authors.affiliation: Reproductive Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India.
authors.forename: Golla Jaya
authors.initials: GJ
authors.lastname: Prakash
authors.forename: Pankaj
authors.initials: P
authors.lastname: Suman
authors.forename: Diana M
authors.initials: DM
authors.lastname: Morales Prieto
authors.forename: Udo R
authors.initials: UR
authors.lastname: Markert
authors.forename: Satish K
authors.initials: SK
authors.lastname: Gupta
mesh_terms: D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D017209:Apoptosis; D002070:Butadienes / Q000494:pharmacology; D002453:Cell Cycle; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D004789:Enzyme Activation; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014327:Trophoblasts / Q000187:drug effects / Q000201:enzymology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000952:Antigens, Polyomavirus Transforming; C494826:BAX protein, human; D002070:Butadienes; D053605:Leukemia Inhibitory Factor; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C113580:U 0126; D051028:bcl-2-Associated X Protein; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3