FGFR3 mutation affects cell growth, apoptosis and attachment in keratinocytes

Hafner, Christian and Di Martino, Erica and Pitt, Eva and Stempfl, Thomas and Tomlinson, Darren and Hartmann, Arndt and Landthaler, Michael and Knowles, Margaret and Vogt, Thomas (2010) FGFR3 mutation affects cell growth, apoptosis and attachment in keratinocytes. EXPERIMENTAL CELL RESEARCH, 316 (12). pp. 2008-2016. ISSN 0014-4827,

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Abstract

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 (C) 2010 Elsevier Inc. All rights reserved

Item Type: Article
Uncontrolled Keywords: BENIGN SKIN TUMORS; FACTOR RECEPTOR-3; SEBORRHEIC KERATOSES; THANATOPHORIC DYSPLASIA; ACTIVATING MUTATIONS; EPIDERMAL NEVI; TRANSMEMBRANE MUTATION; ACANTHOSIS NIGRICANS; MULTIPLE-MYELOMA; PIK3CA MUTATIONS; FGFR3; Keratinocyte; Skin; Cell growth; Apoptosis
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Dermatologie und Venerologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 22 Jul 2020 08:34
Last Modified: 22 Jul 2020 08:34
URI: https://pred.uni-regensburg.de/id/eprint/24459

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