| Autor: |
Diana M. Morales-Prieto, Stephanie Ospina-Prieto, Wittaya Chaiwangyen, Maja Weber, Sebastian Hölters, Ekkehard Schleussner, Justine S. Fitzgerald, Udo R. Markert |
| Jazyk: |
angličtina |
| Rok vydání: |
2013 |
| Předmět: |
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| Zdroj: |
The Scientific World Journal, Vol 2013 (2013) |
| Druh dokumentu: |
article |
| ISSN: |
1537-744X |
| DOI: |
10.1155/2013/259845 |
| Popis: |
Invasiveness of trophoblast and choriocarcinoma cells is in part mediated via leukemia inhibitory factor- (LIF-) induced activation of signal transducer and activator of transcription 3 (STAT3). The regulation of STAT3 phosphorylation at its ser727 binding site, possible crosstalk with intracellular MAPK signaling, and their functional implications are the object of the present investigation. JEG-3 choriocarcinoma cells were cultured in presence/absence of LIF and the specific ERK1/2 inhibitor (U0126). Phosphorylation of signaling molecules (p-STAT3 (ser727 and tyr705) and p-ERK1/2 (thr 202/tyr 204)) was assessed per Western blot. Immunocytochemistry confirmed results, but also pinpointed the location of phosphorylated signaling molecules. STAT3 DNA-binding capacity was studied with a colorimetric ELISA-based assay. Cell viability and invasion capability were assessed by MTS and Matrigel assays. Our results demonstrate that LIF-induced phosphorylation of STAT3 (tyr705 and ser727) is significantly increased after blocking ERK1/2. STAT3 DNA-binding capacity and cell invasiveness are enhanced after LIF stimulation and ERK1/2 blockage. In contrast, proliferation is enhanced by LIF but reduced after ERK1/2 inhibition. The findings herein show that blocking ERK1/2 increases LIF-induced STAT3 phosphorylation and STAT3 DNA-binding capacity by an intranuclear crosstalk, which leads to enhanced invasiveness and reduced proliferation. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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