Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma

Marta Chesi, Leslie A. Brents, Sarah A. Ely, Carlos Bais, Davide F. Robbiani, Enrique A Mesri, W. Michael Kuehl, P. Leif Bergsagel

Research output: Contribution to journalArticle

235 Citations (Scopus)

Abstract

The t(4;14) translocation occurs frequently in multiple myeloma (MM) and results in the simultaneous dysregulated expression of 2 potential oncogenes, FGFR3 (fibroblast growth factor receptor 3) from der(14) and multiple myeloma SET domain protein/Wolf-Hirschhorn syndrome candidate gene 1 from der(4). It is now shown that myeloma cells carrying a t(4;14) translocation express a functional FGFR3 that in some cases is constitutively activated by the same mutations that cause thanatophoric dysplasia. As with activating mutations of K-ras and N-ras, which are reported in approximately 40% of patients with MM, activating mutations of FGFR3 occur during tumor progression. However, the constitutive activation of ras and FGFR3 does not occur in the same myeloma cells. Thus the activated forms of these proteins appear to share an overlapping role in tumor progression, suggesting that they also share the signaling cascade. Consistent with this prediction, it is Shown that activated FGFR3 - when expressed at levels similar to those seen in t(4;14) myeloma - is an oncogene that acts through the MAP kinase pathway to transform NIH 3T3 cells, which can then generate tumors in nude mice; Thus, FGFR3, when overexpressed in MM, may be not only oncogenic when stimulated by FGF ligands in the bone marrow microenvironment, but is also a target for activating mutations that enable FGFR3 to play a ras-like role in tumor progression.

Original languageEnglish
Pages (from-to)729-736
Number of pages8
JournalBlood
Volume97
Issue number3
DOIs
StatePublished - Feb 1 2001
Externally publishedYes

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Receptor, Fibroblast Growth Factor, Type 3
Multiple Myeloma
Oncogenes
Tumors
Neoplasms
Mutation
Thanatophoric Dysplasia
Wolf-Hirschhorn Syndrome
NIH 3T3 Cells
Nude Mice
Bone
Proteins
Phosphotransferases
Genes
Bone Marrow
Chemical activation
Ligands

ASJC Scopus subject areas

  • Hematology

Cite this

Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma. / Chesi, Marta; Brents, Leslie A.; Ely, Sarah A.; Bais, Carlos; Robbiani, Davide F.; Mesri, Enrique A; Kuehl, W. Michael; Bergsagel, P. Leif.

In: Blood, Vol. 97, No. 3, 01.02.2001, p. 729-736.

Research output: Contribution to journalArticle

Chesi, M, Brents, LA, Ely, SA, Bais, C, Robbiani, DF, Mesri, EA, Kuehl, WM & Bergsagel, PL 2001, 'Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma', Blood, vol. 97, no. 3, pp. 729-736. https://doi.org/10.1182/blood.V97.3.729
Chesi, Marta ; Brents, Leslie A. ; Ely, Sarah A. ; Bais, Carlos ; Robbiani, Davide F. ; Mesri, Enrique A ; Kuehl, W. Michael ; Bergsagel, P. Leif. / Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma. In: Blood. 2001 ; Vol. 97, No. 3. pp. 729-736.
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