Inhibition of Platelet-derived Growth Factor-induced Cell Growth Signaling by a Short Interfering RNA for EWS-Fli1 via Down-regulation of Phospholipase D2 in Ewing Sarcoma Cells
Copyright policy )Inhibition of Platelet-derived Growth Factor-induced Cell Growth Signaling by a Short Interfering RNA for EWS-Fli1 via Down-regulation of Phospholipase D2 in Ewing Sarcoma Cells
EWS-Fli1, a fusion gene resulting from a chromosomal translocation t(11;22, q24;q12) and found in Ewing sarcoma and primitive neuroectodermal tumors, encodes a transcriptional activator and promotes cellular transformation. However, the precise biological functions of its products remain unknown. To investigate the role of EWS-Fli1 in cell growth signaling, we transfected Ewing sarcoma TC-135 cells with short interfering RNAs for EWS-Fli1. EWS-Fli1 knockdown reduced cell growth and platelet-derived growth factor (PDGF)-BB-induced activation of the growth signaling enzymes. Interestingly, phospholipase D2 (but not the PDGF-BB receptor) showed marked down-regulation in the EWS-Fli1-knocked down TC-135 cells compared with the control cells. In Ewing sarcoma TC-135 cells, the PDGF-BB-induced phosphorylation of growth signaling involving extracellular signal-regulated kinase, Akt, p70S6K, and the expression of cyclin D3 were markedly inhibited by transfection with short interfering RNA phospholipase (PL)-D2. The PDGF-BB-induced activation of growth signaling was also suppressed by 1-butanol, which prevents the production of phosphatidic acid by phospholipase D (but not by t-butyl alcohol), thereby implicating PLD2 in PDGF-BB-mediated signaling in TC-135 cells. These results suggest that EWS-Fli1 may play a role in the regulation of tumor proliferation-signaling enzymes via PLD2 expression in Ewing sarcoma cells.
- Gifu University Japan
Platelet-Derived Growth Factor, Dose-Response Relationship, Drug, Oncogene Proteins, Fusion, Proto-Oncogene Protein c-fli-1, Blotting, Western, Becaplermin, Down-Regulation, Proto-Oncogene Proteins c-sis, Models, Biological, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Cyclins, Phospholipase D, Humans, Cyclin D3, Enzyme Inhibitors, Phosphorylation, RNA, Small Interfering, RNA-Binding Protein EWS, Cell Proliferation
Platelet-Derived Growth Factor, Dose-Response Relationship, Drug, Oncogene Proteins, Fusion, Proto-Oncogene Protein c-fli-1, Blotting, Western, Becaplermin, Down-Regulation, Proto-Oncogene Proteins c-sis, Models, Biological, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Cyclins, Phospholipase D, Humans, Cyclin D3, Enzyme Inhibitors, Phosphorylation, RNA, Small Interfering, RNA-Binding Protein EWS, Cell Proliferation
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