Objectives: Fibroblast growth factor receptor 3 (FGFR3) is a proto-oncogene that is often dysregulated together with multiple myeloma SET-domain (MMSET) by the immunoglobulin heavy chain (IGH) gene in t(4;14)(pos) multiple myeloma (MM) cells, and which is usually not expressed in MM cells without this translocation. Whether FGFR3 may play a role in MM cells without t(4;14) and the IGH-MMSET fusion protein is unclear and is the focus of this report.
Methods: FGFR3 expression was explored in cell lines with and without t(4;14) by fluorescence in situ hybridization (FISH), RT-PCR and Western Blot. FGFR3 inhibitors SU5402 and PD173074 were used to explore the role of FGFR3 in these cells.
Results: We discovered an amplification of the FGFR3 locus in INA-6, a human MM cell line. We also demonstrated expression of FGFR3 mRNA and protein in the cells, probably caused by the extra copy of the gene. INA-6 cells did not have t(4;14) and neither was there any involvement of the other IG loci in translocations with the FGFR3 gene. The FGFR3 inhibitors decreased the proliferation of INA-6.
Conclusion: The decreased viability and proliferation in INA-6, following inhibition with FGFR3 inhibitors, indicates that FGFR3 may play a role also in cells without t(4;14) - and hence without high expression of MMSET, the ubiquitous oncoprotein in MM cells with t(4;14). This gives further credibility to the notion that FGFR3 expression is not just an epiphenomenon in t(4;14) MM, but an important part of the malignant phenotype.