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  • Title: Bortezomib therapeutic effect is associated with expression of FGFR3 in multiple myeloma cells.
    Author: Guan M, Zhu L, Somlo G, Hughes A, Zhou B, Yen Y.
    Journal: Anticancer Res; 2009 Jan; 29(1):1-9. PubMed ID: 19331127.
    Abstract:
    UNLABELLED: The ectopically expressed and deregulated fibroblast growth factor receptor 3 (FGFR3) has been observed in approximately 20% of multiple myeloma (MM) patients. In this study, we investigated whether the therapeutic effect of bortezomib is associated with FGFR3 expression. MATERIALS AND METHODS: Cell proliferation and apoptosis assays were performed in minimal FGFR3 expressing U266 cells and compared to U266 cells overexpressing FGFR3 wild-type (T-U266), or Y373C (Y-U266) or K650E (K-U266) mutant FGFR3. RESULTS: Our results suggested cell survival decreases in a dose-dependent manner. Interestingly, expression of FGFR3 protein was similarly dose dependent on bortezomib. It is confirmed the bortezomib-induced apoptotic death is correlated with FGFR3 expression. Furthermore, increased expression of p-STAT3, Mcl-1 and VEGF suggested that bortezomib resistance associated with Y373C mutation and wild-type FGFR3 may be partly mediated through p-STAT3 signaling. CONCLUSION: Our data indicates that Y373C mutation and wild-type FGFR3 may be associated with bortezomib-related treatment resistance in multiple myeloma.
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