| FGFR3 is expressed and is important for survival in INA-6, a human myeloma cell line without a t(4;14). | |
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MedLine Citation:
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PMID: 19594619 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Thea K Våtsveen; Anne-Tove Brenne; Hong Y Dai; Anders Waage; Anders Sundan; Magne Børset |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-07-06 |
Journal Detail:
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Title: European journal of haematology Volume: 83 ISSN: 1600-0609 ISO Abbreviation: Eur. J. Haematol. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-14 Completed Date: 2009-11-06 Revised Date: 2012-06-05 |
Medline Journal Info:
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Nlm Unique ID: 8703985 Medline TA: Eur J Haematol Country: England |
Other Details:
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Languages: eng Pagination: 471-6 Citation Subset: IM |
Affiliation:
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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 |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line, Tumor Cell Proliferation Cell Survival / genetics Chromosomes, Human, Pair 14* Chromosomes, Human, Pair 4* Gene Dosage / genetics Gene Expression Regulation, Neoplastic* Humans In Situ Hybridization, Fluorescence Multiple Myeloma / genetics, metabolism*, pathology Quantitative Trait Loci / genetics Receptor, Fibroblast Growth Factor, Type 3 / biosynthesis*, genetics Reverse Transcriptase Polymerase Chain Reaction Translocation, Genetic* |
| Chemical | |
Reg. No./Substance:
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EC 2.7.10.1/FGFR3 protein, human; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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