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

Min Guan1, Lijun Zhu, George Somlo

  • 1Department of Clinical Molecular Pharmacology, Division of Medical Oncology and Therapeutic Research, City of Hope National Medical Center, Duarte, CA, 91010, USA.

Anticancer Research
|April 1, 2009
PubMed
Abstract

Insights

Fibroblast growth factor receptor 3 (FGFR3) expression correlates with bortezomib efficacy in multiple myeloma. Elevated FGFR3, particularly Y373C mutations, may indicate resistance to bortezomib treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Hematology

Background:

  • Fibroblast growth factor receptor 3 (FGFR3) is deregulated in about 20% of multiple myeloma (MM) cases.
  • The role of FGFR3 expression in MM treatment response remains unclear.

Purpose of the Study:

  • To investigate the association between FGFR3 expression and the therapeutic efficacy of bortezomib in multiple myeloma.
  • To determine if specific FGFR3 mutations influence bortezomib response.

Main Methods:

  • Cell proliferation and apoptosis assays were conducted.
  • U266 cells with varying levels of FGFR3 expression (wild-type, Y373C mutant, K650E mutant) were utilized.
  • Western blotting was used to assess protein expression levels.

Main Results:

  • Bortezomib treatment reduced cell survival in a dose-dependent manner.
  • FGFR3 protein expression levels were also dose-dependent on bortezomib.
  • Bortezomib-induced apoptosis was correlated with FGFR3 expression.
  • Increased p-STAT3, Mcl-1, and VEGF expression suggested bortezomib resistance associated with Y373C mutation and wild-type FGFR3, potentially mediated by p-STAT3 signaling.

Conclusions:

  • FGFR3 expression, including wild-type and Y373C mutations, is linked to bortezomib resistance in multiple myeloma.
  • The p-STAT3 signaling pathway may play a role in mediating this resistance.