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SHR Neuro Krebs Kardio Lipid

Rauh, A; Windischhofer, W; Kovacevic, A; Devaney, T; Huber, E; Semlitsch, M; Leis, HJ; Sattler, W; Malle, E.
Endothelin (ET)-1 and ET-3 promote expression of c-fos and c-jun in human choriocarcinoma via ET(B) receptor-mediated G(i)- and G(q)-pathways and MAP kinase activation.
Br J Pharmacol. 2008; 154(1): 13-24. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Devaney Trevor
Kovacevic Alenka
Leis Hans-Jörg
Malle Ernst
Rauh Anamaria
Sattler Wolfgang
Semlitsch Michaela
Windischhofer Werner
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Number of Figures: 10
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Abstract:
Endothelins (ETs) and their G protein-coupled receptors exert key physiological functions during normal and aberrant placental development. Trophoblast cells mediate the contact between the embryo and the mother, by establishing a transient organ, the placenta. Choriocarcinoma cells display many of the biochemical and morphological characteristics of in utero invasive trophoblast cells and may therefore be used as a suitable model to study epithelial tumour progression of foetal-derived cells. The present study aimed at investigating ET receptor-mediated activation of the mitogen-activated protein kinase (MAPK) pathway in human choriocarcinoma. Both JAR and Jeg-3 choriocarcinoma cell lines expressed ET receptor subtype B (ET(B)) but not ET(A) receptor transcripts. ET(B) receptor engagement by ET-1 and ET-3 resulted in a similar time- and concentration-dependent phosphorylation of p42/44 MAPK, also known as extracellular regulated kinase 1/2. Using specific pharmacological antagonists/inhibitors, we showed that ET-1/-3-mediated signal transduction by the ET(B) receptor is transmitted via G(i)- and G(q)-dependent pathways through activation of the Src (G(i)) and protein kinase C (G(q)) axis that converge at Ras/Raf, leading to downstream activation of p42/44. On a functional level, ET(B) engagement and subsequent phosphorylation of p42/44 resulted in enhanced transcription of the immediate early response genes c-fos and c-jun, a process commonly assumed to be mediated by the ET(A) receptor, and increased cell growth and relative cell area. As human choriocarcinoma cells secrete ETs, pharmacological antagonism of ETs and/or ET(B) receptor-mediated signal transduction could represent a likely target therapy for choriocarcinoma.
Find related publications in this database (using NLM MeSH Indexing)
Blotting, Western -
Cell Count -
Cell Line, Tumor -
Cell Movement - drug effects
Choriocarcinoma - genetics
DNA Primers -
Endothelin-1 - pharmacology
Endothelin-3 - pharmacology
GTP-Binding Protein alpha Subunits, Gi-Go - physiology
GTP-Binding Protein alpha Subunits, Gq-G11 - physiology
Gene Expression - drug effects
Genes, fos - drug effects
Genes, jun - drug effects
Humans -
Mitogen-Activated Protein Kinases - physiology
RNA - biosynthesis
Receptor, Endothelin B - genetics
Reverse Transcriptase Polymerase Chain Reaction -
Signal Transduction - drug effects
Tetrazolium Salts -
Thiazoles -

Find related publications in this database (Keywords)
trophoblast
intracellular signal transmission
tumour cell growth
G-protein coupled receptor
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