Leukaemia inhibitory factor mediated proliferation of HTR-8/SVneo trophoblast cells is dependent on activation of extracellular signal-regulated kinase 1/2
Golla Jaya Prakash A C , Pankaj Suman A C , Diana M. Morales Prieto B , Udo R. Markert B and Satish K. Gupta A DA Reproductive Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India.
B Placenta Laboratory, Department of Obstetrics, Faculty of Medicine, Friedrich-Schiller University Jena, D-07743 Jena, Germany.
C These authors contributed equally to this work.
D Corresponding author. Email: skgupta@nii.res.in
Reproduction, Fertility and Development 23(5) 714-724 https://doi.org/10.1071/RD10315
Submitted: 24 November 2010 Accepted: 24 December 2010 Published: 17 May 2011
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 G2/M phase of cell cycle. Stimulation with LIF resulted in the activation of both signal transducer and activator of transcription (STAT) 3 Tyr705 and ERK1/2, but inhibition of ERK1/2 signalling by pretreatment of cells with U0126 (10 µM) for 2 h resulted in abrogation of LIF-mediated increases in G2/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.
Additional keywords: apoptosis, trophoblast.
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