The expression of keratinocyte growth factor receptor (FGFR2-IIIb) correlates with the high proliferative rate of HaCaT keratinocytes.
Keratinocyte growth factor receptor (KGFR = FGFR2-IIIb) is a tyrosine kinase receptor expressed by keratinocytes, which mediates the effects of fibroblast growth factors (FGF). There are contradictory data in the literature regarding the role of FGFR2-IIIb during the proliferation/differentiation programme of keratinocytes. In this study, we aimed to investigate whether overexpression of FGFR2-IIIb may have a role in the regulation of keratinocyte proliferation. We analysed the expression of FGFR2-IIIb in an in vitro HaCaT model system representing different stages of proliferation and differentiation of keratinocytes. Real-time RT-PCR and Western blot analyses demonstrated a correlation between FGFR2-IIIb mRNA and protein expression and the proportion of cells in S/G2/M phase in synchronized HaCaT keratinocytes and thus with proliferation activity (r = 0.96). After treatment with the antipsoriatic drug, dithranol, FGFR2-IIIb is downregulated dose dependently both at mRNA and protein levels. Moreover, when the rate of proliferation is decreased by the lack of cell attachment to the culturing surface, FGFR2-IIIb mRNA (P = 0.0315) and protein expressions were also reduced (P = 0.0242), while a differentiation marker, keratin 10, mRNA (P = 0.0003) and protein levels (P = 0.001) were increased (r = -0.92). Based on our results we conclude that FGFR2-IIIb expression in HaCaT keratinocytes corresponds with the proliferative activation of the cells and is not related to the differentiation programme.
Nagy
Nikoletta
N
Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.
Bata-Csörgo
Zsuzsanna
Z
Kopasz
Norbert
N
Szeg
Csilla
C
Pivarcsi
Andor
A
Koreck
Andrea
A
Dobozy
Attila
A
Kemény
Lajos
L
Széll
Márta
M
D000875:Anthralin / Q000494:pharmacology; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D008957:Models, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000096:biosynthesis* / Q000502:physiology; D013997:Time Factors
D012333:RNA, Messenger; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor; D000875:Anthralin