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

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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-κB p65 suggested that bortezomib resistance associated with Y373C mutation and wild-type FGFR3 may be partly mediated through Bcl-2 and NF-κB 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.

Original languageEnglish
Pages (from-to)1921-1930
Number of pages10
JournalAnticancer Research
Volume30
Issue number6
Publication statusPublished - Jun 1 2010
Externally publishedYes

Keywords

  • Bortezomib
  • Fibroblast growth factor receptor 3 (FGFR3)
  • Lymphoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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