Bortezomib therapeutic effect is associated with expression of FGFR3 in multiple myeloma cells.
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.


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.


CONCLUSIONS
Our data indicates that Y373C mutation and wild-type FGFR3 may be associated with bortezomib-related treatment resistance in multiple myeloma.
Guan
Min
M
Department of Clinical Molecular Pharmacology, Division of Medical Oncology and Therapeutic Research, City of Hope National Medical Center, Duarte, CA, 91010, USA.
Zhu
Lijun
L
Somlo
George
G
Hughes
Alison
A
Zhou
Bingsen
B
Yen
Yun
Y