scholarly journals Fibroblast Growth Factor Receptor 3 (FGFR3)–Analyses of the S249C Mutation and Protein Expression in Primary Cervical Carcinomas

2001 ◽  
Vol 23 (2) ◽  
pp. 45-49 ◽  
Author(s):  
Haiyan Dai ◽  
Ruth Holm ◽  
Gunnar B. Kristensen ◽  
Vera M. Abeler ◽  
Anne‐Lise Børresen‐Dale ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Bone Development ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Activating Mutations ◽  
Cervical Carcinomas ◽  
Fgfr3 Gene ◽  
Protein Staining

Fibroblast growth factor receptor 3 (FGFR3) seems to play an inhibitory role in bone development, as activating mutations in the gene underlie disorders such as achondroplasia and thanatophoric dysplasia. Findings from multiple myeloma (MM) indicate that FGFR3 also can act as an oncogene, and mutation of codon 249 in the fibroblast growth factor receptor 3 (FGFR3) gene was recently detected in 3/12 primary cervical carcinomas. We have analysed 91 cervical carcinomas for this specific S249C mutation using amplification created restriction site methodology (ACRS), and detected no mutations. Immunohistochemistry was performed on 73 of the tumours. Reduced protein staining was seen in 43 (58.8%) samples. Six of the tumours (8.2%) revealed increased protein staining compared with normal cervical tissue. These patients had a better prognosis than those with reduced or normal levels, although not statistically significant. This report weakens the hypothesis of FGFR3 as an oncogene of importance in cervical carcinomas.

Inhibition of fibroblast growth factor receptor 3 induces differentiation and apoptosis in t(4;14) myeloma

Blood ◽  
2004 ◽  
Vol 103 (9) ◽  
pp. 3521-3528 ◽  
Author(s):  
Suzanne Trudel ◽  
Scott Ely ◽  
Yildiz Farooqi ◽  
Maurizio Affer ◽  
Davide F. Robbiani ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Myeloma Cell ◽  
Fibroblast Growth ◽  
Genetic Changes ◽  
Functional Changes ◽  
Activating Mutations ◽  
Molecule Inhibitor

Abstract We have previously shown that dysregulation of fibroblast growth factor receptor 3 (FGFR3) by the t(4;14) translocation is a primary event in multiple myeloma (MM) and that activating mutations of FGFR3 are acquired in some cases. We describe here inhibition of wild-type (WT) and constitutively activated mutant FGFR3 autophosphorylation by the small molecule inhibitor, PD173074. Inhibition of FGFR3 in human myeloma cell lines was associated with decreased viability and tumor cell growth arrest. Further, morphologic, phenotypic, and functional changes typical of plasma cell (PC) differentiation, including increase in light-chain secretion and expression of CD31, were observed and this was followed by apoptosis. Finally, using a mouse model of FGFR3 myeloma, we demonstrate a delay in tumor progression and prolonged survival of mice treated with PD173074. These results indicate that inhibition of FGFR3, even in advanced disease associated with multiple genetic changes, may allow the cell to complete its developmental program and render it sensitive to apoptotic signals. In addition, this represents the validation of a therapeutic target in MM that may benefit patients who have a very poor prognosis with currently available treatments. (Blood. 2004;103:3521-3528)

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