Bortezomib Therapeutic Effect Is Associated with Expression and Mutation of FGFR3 in Human Lymphoma Cells

作者：Zheng, Weiyan; Guan, Min; Zhu, Lijun; Cai, Zhen; Chung, Vincent; Huang, He; Yen, Yun

来源：Anticancer Research, 2010, 30(6): 1921-1930.

• Bortezomib
• fibroblast growth factor receptor 3 (FGFR3)
• lymphoma

Objective: 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. Materials and Methods: 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: 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-kappa B p65 suggested that bortezomib resistance associated with Y373C mutation and wild-type FGFR3 may be partly mediated through Bcl-2 and NF-kappa B signaling. Conclusion: Data from this study indicate that mutation status and the expression level of FGFR3 may be associated with bortezomib-related treatment resistance in lymphoma.

• 出版日期2010-6
• 单位浙江大学