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- W2042926648 abstract "Abstract Bladder cancer is estimated to be the fifth most prevalent type of cancer in industrialized countries. In most of the cases (more than 90 %), tumors are urothelial cell carcinoma (UCC). Activating mutations of the fibroblast growth factor receptor 3 (FGFR3) are the most frequent genetic alteration in UCC (up to 80% in low grade Ta tumors). We have previously described that the mutated receptor displays oncogenic properties (Bernard-Pierrot et al., 2006). In this study, we aimed to better understand the signaling properties of the oncogenic mutated FGFR3. We performed a systematic analysis of phosphoproteins involved in classical signaling pathways activated by FGFRs coupled to a pharmacological study in NIH-3T3 cells expressing the mutated receptor or not. We identified p38 MAPK as a key down-stream signaling molecule of FGFR3-induced NIH-3T3 cell transformation. We further showed that activation of p38 is also critical for FGFR3-induced tumorigenesis of epithelial cells. Indeed, in vitro, p38- siRNAs and SB203580, a specific p38 MAPK inhibitor, inhibited the transforming properties of MGH-U3 cells derived from a human bladder tumor and expressing mutated FGFR3. Moreover, in vivo, treatment with SB203580, inhibited mutated FGFR3-induced proliferation both in MGH-U3 xenografted tumors and in transgenic mice expressing mutated FGFR3 in the skin (Logié et al.,2005). Finally, we identified p38 activation in all FGFR3 mutated human bladder tumors studied and more generally in all human bladder tumors presenting identified FGFR3 signaling pathway alterations. Taken together, those results suggest that p38 is a key signaling molecule in a high proportion of human bladder tumors and could represent an interesting therapeutic target both in muscle non-invasive and invasive tumors mutated for FGFR3 or more generally in tumors with FGFR3 pathway activation. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B92." @default.
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- W2042926648 date "2009-12-01" @default.
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- W2042926648 title "Abstract B92: P38 MAPK activation is critical for FGFR3‐induced cell transformation in human bladder carcinoma" @default.
- W2042926648 doi "https://doi.org/10.1158/1535-7163.targ-09-b92" @default.
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