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SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
Doi: 10.1038/bjp.2008.92
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- Führende Autor*innen der Med Uni Graz
- Malle Ernst
- Rauh Anamaria
- Windischhofer Werner
- Co-Autor*innen der Med Uni Graz
- DeVaney Trevor
- Huber Evelyn
- Kovacevic Alenka
- Leis Hans-Joerg
- Sattler Wolfgang
- Semlitsch Michaela
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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
- RNA - isolation & purification
- Receptor, Endothelin B - genetics
- Reverse Transcriptase Polymerase Chain Reaction -
- Signal Transduction - drug effects
- Signal Transduction - physiology
- Tetrazolium Salts -
- Thiazoles -
- Find related publications in this database (Keywords)
- trophoblast
- intracellular signal transmission
- tumour cell growth
- G-protein coupled receptor