Leukaemia inhibitory factor mediated proliferation of HTR-8/SVneo trophoblast cells is dependent on activation of extracellular signal-regulated kinase 1/2

2011 ◽  
Vol 23 (5) ◽  
pp. 714 ◽  
Author(s):  
Golla Jaya Prakash ◽  
Pankaj Suman ◽  
Diana M. Morales Prieto ◽  
Udo R. Markert ◽  
Satish K. Gupta

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.

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Naguib Salleh ◽  
Nelli Giribabu

Leukaemia inhibitory factor (LIF) plays an indispensible role in embryo implantation. Aberrant LIF production is linked to implantation failure. LIF regulates multiple processes prior to and during implantation such as uterine transformation into a receptive state, decidualization, blastocyst growth and development, embryo-endometrial interaction, trophoblast invasion, and immune modulation. Due to its critical role, LIF has been a target for a nonhormonal contraception. In this review, we summarize up-to-date information on the role of LIF in implantation and its role in contraception.


2000 ◽  
Vol 275 (37) ◽  
pp. 28793-28801 ◽  
Author(s):  
Frédéric Blanchard ◽  
Laurence Duplomb ◽  
Yanping Wang ◽  
Olivier Robledo ◽  
Erin Kinzie ◽  
...  

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5503-5513 ◽  
Author(s):  
Haruhiko Kanasaki ◽  
Gregoy Y. Bedecarrats ◽  
Kyung-Yoon Kam ◽  
Shuyun Xu ◽  
Ursula B. Kaiser

The pattern of GnRH release is associated with differential synthesis and release of LH and FSH. Using a perifusion system, we previously reported that stimulation of the LβT2 cell line with varying GnRH pulse frequencies resulted in differential stimulation of LHβ and FSHβ gene transcription, analogous to previous observations in primary gonadotropes. In the present study, we investigated the patterns of MAPK activation by GnRH and the role of MAPK in mediating the frequency-dependent effects. In static culture, ERK activation in LβT2 cells stimulated with continuous GnRH (10 nm) was maximal by 10 min and persisted for up to 6 h, with a return to basal levels by 20 h. In contrast, stimulation with continuous GnRH (10 nm) in perifused cells resulted in a more sustained activation of ERK. To investigate the effects of GnRH pulse frequency on ERK activation, perifused LβT2 cells were stimulated with pulsatile GnRH at a frequency of one pulse every 30 min or one pulse every 2 h for 20 h (10 nm, 5 min/pulse). After the final GnRH pulse, cells were lysed at frequent intervals and levels of ERK phosphorylation were measured. Under high-frequency conditions, ERK activation was maximal 10 min after the GnRH pulse and returned to baseline levels by 20 min. In contrast, under lower GnRH pulse frequency conditions, ERK activation occurred more rapidly and activation was more sustained, with a slower rate of ERK dephosphorylation. These changes resulted in different levels of nuclear phosphorylated ERK. Blockade of ERK activation abolished GnRH-dependent activation of LHβ and FSHβ transcription at both high and low pulse frequencies. These results demonstrate that in perifused LβT2 cells, distinct patterns of ERK activation/inactivation are regulated by GnRH pulse frequency, and the difference in ERK activation may be important for GnRH pulse frequency-dependent differential stimulation of LHβ and FSHβ gene expression.


2012 ◽  
Vol 40 (1) ◽  
pp. 251-256 ◽  
Author(s):  
Pamela A. Lochhead ◽  
Rebecca Gilley ◽  
Simon J. Cook

The MEK5 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 5]/ERK5 pathway is the least well studied MAPK signalling module. It has been proposed to play a role in the pathology of cancer. In the present paper, we review the role of the MEK5/ERK5 pathway using the ‘hallmarks of cancer’ as a framework and consider how this pathway is deregulated. As well as playing a key role in endothelial cell survival and tubular morphogenesis during tumour neovascularization, ERK5 is also emerging as a regulator of tumour cell invasion and migration. Several oncogenes can stimulate ERK5 activity, and protein levels are increased by a novel amplification at chromosome locus 17p11 and by down-regulation of the microRNAs miR-143 and miR-145. Together, these finding underscore the case for further investigation into understanding the role of ERK5 in cancer.


2005 ◽  
Vol 68 (2) ◽  
pp. 421-429 ◽  
Author(s):  
Vincent Pascoli ◽  
Emmanuel Valjent ◽  
Anne-Gaëlle Corbillé ◽  
Jean-Christophe Corvol ◽  
Jean-Pol Tassin ◽  
...  

Placenta ◽  
2021 ◽  
Vol 114 ◽  
pp. 139
Author(s):  
Jumpei Terakawa ◽  
Kazuhiro Matsuo ◽  
Takafumi Namiki ◽  
Kana Ohtomo ◽  
Atsuko Kageyama ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document