PMID- 19594619
OWN - NLM
STAT- MEDLINE
DCOM- 20091106
LR  - 20211203
IS  - 1600-0609 (Electronic)
IS  - 0902-4441 (Linking)
VI  - 83
IP  - 5
DP  - 2009 Nov
TI  - FGFR3 is expressed and is important for survival in INA-6, a human myeloma cell 
      line without a t(4;14).
PG  - 471-6
LID - 10.1111/j.1600-0609.2009.01312.x [doi]
AB  - 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.
FAU - Vatsveen, Thea K
AU  - Vatsveen TK
AD  - 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
FAU - Brenne, Anne-Tove
AU  - Brenne AT
FAU - Dai, Hong Y
AU  - Dai HY
FAU - Waage, Anders
AU  - Waage A
FAU - Sundan, Anders
AU  - Sundan A
FAU - Borset, Magne
AU  - Borset M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090706
PL  - England
TA  - Eur J Haematol
JT  - European journal of haematology
JID - 8703985
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
RN  - EC 2.7.10.1 (FGFR3 protein, human)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 3)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cell Survival/genetics
MH  - *Chromosomes, Human, Pair 14
MH  - *Chromosomes, Human, Pair 4
MH  - Gene Dosage/genetics
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Multiple Myeloma/genetics/*metabolism/pathology
MH  - Proto-Oncogene Mas
MH  - Quantitative Trait Loci/genetics
MH  - Receptor, Fibroblast Growth Factor, Type 3/*biosynthesis/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Translocation, Genetic
EDAT- 2009/07/15 09:00
MHDA- 2009/11/07 06:00
CRDT- 2009/07/15 09:00
PHST- 2009/07/15 09:00 [entrez]
PHST- 2009/07/15 09:00 [pubmed]
PHST- 2009/11/07 06:00 [medline]
AID - EJH1312 [pii]
AID - 10.1111/j.1600-0609.2009.01312.x [doi]
PST - ppublish
SO  - Eur J Haematol. 2009 Nov;83(5):471-6. doi: 10.1111/j.1600-0609.2009.01312.x. Epub 
      2009 Jul 6.