PMID: 20651335Jul 24, 2010Paper

Bortezomib therapeutic effect is associated with expression and mutation of FGFR3 in human lymphoma cells

Anticancer Research
Weiyan ZhengYun Yen

Abstract

Ectopically expressed and deregulated fibroblast growth factor receptor 3 (FGFR3) has been observed in many malignant cancer patients, including those with lymphoma. This study investigated whether the therapeutic effect of bortezomib in lymphoma is associated with FGFR3-expression. Cell proliferation and apoptosis assays were performed in minimal FGFR3 expressing U937 cells and compared to U937 cells overexpressing FGFR3 wild-type, or Y373C or K650E mutant FGFR3. Results from this study suggested the expression of FGFR3 protein is associated with the therapeutic effect of bortezomib. It was observed that bortezomib-induced apoptotic death is correlated with FGFR3 expression. U937 cells overexpression of wild-type FGFR3 demonstrated resistance to bortezomib treatment. U937 cells expressing Y373C mutated FGFR3 showed an almost equal resistance to bortezomib as U937 cells expressing wild-type FGFR3. U937 cells expressing mutated K650E FGFR3 showed more sensitivity to bortezomib than did the parental U937 cells. Furthermore, increased expression of Mcl-1 and decreased expression of NF-kappaB p65 suggested that bortezomib resistance associated with Y373C mutation and wild-type FGFR3 may be partly mediated through Bcl-2 and NF-kappa...Continue Reading

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