FGFR3 is expressed and is important for survival in INA-6, a human myeloma cell line without a t(4;14).
OBJECTIVE
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.


CONCLUSIONS
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.
Våtsveen
Thea K
TK
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Olav Kyrres gt. 9, N-7489 Trondheim, Norway. thea.k.vatsveen@ntnu.no
Brenne
Anne-Tove
AT
Dai
Hong Y
HY
Waage
Anders
A
Sundan
Anders
A
Børset
Magne
M
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002883:Chromosomes, Human, Pair 14; D002894:Chromosomes, Human, Pair 4; D018628:Gene Dosage / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000090063:Proto-Oncogene Mas; D040641:Quantitative Trait Loci / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3