Activation of the beta-catenin signaling pathway and its impact on RPE cell cycle.
OBJECTIVE
To investigate the effect of EGF, IGF-1, and VEGF on ARPE19 cell proliferation and differentiation.


METHODS
The gene expression of RPE-specific differentiation and proliferation markers and the transcriptional and translational activity of beta-catenin signaling markers were measured by flow cytometry and RT-PCR.


RESULTS
The data showed a significant decrease in RPE65, CRALBP, and cytokeratin 18 in ARPE-19 cells stimulated with EGF and IGF-1. In addition, a significant decrease in GSK-3beta and beta-catenin was observed that was paralleled by an increase in cyclin D1 expression. Cell cycle studies revealed an increase in ARPE cells in the S-G(2)/M-phase after treatment with EGF or IGF-1. VEGF, on the other hand, led to a reduction in cyclin D1 and to an increase in GSK 3beta and beta-catenin expression which was paralleled by an increase in RPE-specific differentiation markers.


CONCLUSIONS
The data demonstrate the induction of proliferation by EGF and IGF-1 and upregulation of the beta-catenin signaling pathway in ARPE-19 cells. The data suggest that activation of the beta-catenin signaling pathway may be key in activating ARPE-19 cells by different growth factors.
Department of Ophthalmology, Ludwig Boltzmann Institute for Retinology and Biomicroscopic Lasersurgery, Rudolf Foundation Clinic, Vienna, Austria.
Kerstin
K
Steindl-Kuscher
Walter
W
Krugluger
Michael E
ME
Boulton
Paulina
P
Haas
Karl
K
Schrattbauer
Hans
H
Feichtinger
Wolfram
W
Adlassnig
Susanne
S
Binder
D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism*
D015415:Biomarkers; D018797:Cell Cycle Proteins; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I