Document Detail


FGFR3 mutation affects cell growth, apoptosis and attachment in keratinocytes.
MedLine Citation:
PMID:  20420824     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
FGFR3 mutations have recently been identified in several benign epidermal skin lesions such as seborrheic keratosis, epidermal nevus and solar lentigo. The functional consequences of these mutations in human skin are as yet unknown. In this study we analyzed the functional effects of the most common FGFR3 mutation in benign skin tumors, the R248C FGFR3 hotspot mutation, in human HaCaT keratinocytes. The cells were stably transduced with either the R248C or wildtype FGFR3 IIIb cDNA using a retroviral vector system. FGFR3 mutant and wildtype cells showed similar growth rates at subconfluence. However, at confluence FGFR3 mutant keratinocytes revealed a significantly higher cell number than wildtype cells. Furthermore, FGFR3 mutant cells showed significantly lower levels of apoptosis and decreased attachment to fibronectin compared with FGFR3 wildtype cells. Expression of mutant FGFR3 did not alter migration and senescence. Microarray analysis revealed only a few differentially expressed genes between FGFR3 mutant and wildtype keratinocytes. Enhanced phosphorylation of ERK1/2 was observed in confluent R248C mutant HaCaT cells compared with wildtype keratinocytes. Our results suggest that an increased cell number at confluence along with a decreased apoptosis may contribute to the development of acanthotic tumors in FGFR3 mutant skin in vivo.
Authors:
Christian Hafner; Erica Di Martino; Eva Pitt; Thomas Stempfl; Darren Tomlinson; Arndt Hartmann; Michael Landthaler; Margaret Knowles; Thomas Vogt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-24
Journal Detail:
Title:  Experimental cell research     Volume:  316     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-05-31     Completed Date:  2010-06-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2008-16     Citation Subset:  IM    
Affiliation:
Department of Dermatology, University of Regensburg, Regensburg, Germany. christian.hafner@klinik.uni-regensburg.de
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / genetics*
Cell Adhesion
Cell Proliferation
Humans
Keratinocytes / metabolism*
Mutation*
Phosphorylation
Receptor, Fibroblast Growth Factor, Type 3 / genetics*,  metabolism
Chemical
Reg. No./Substance:
EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 3

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