Activation of the beta-catenin signaling pathway and its impact on RPE cell cycle

Invest Ophthalmol Vis Sci. 2009 Sep;50(9):4471-6. doi: 10.1167/iovs.08-3139. Epub 2009 Apr 15.

Abstract

Purpose: 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.

MeSH terms

  • Biomarkers / metabolism
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Epidermal Growth Factor / pharmacology
  • Flow Cytometry
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • RNA, Messenger / metabolism
  • Retinal Pigment Epithelium / cytology*
  • Retinal Pigment Epithelium / drug effects
  • Retinal Pigment Epithelium / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • Up-Regulation / physiology
  • Vascular Endothelial Growth Factor A / pharmacology
  • beta Catenin / metabolism*

Substances

  • Biomarkers
  • Cell Cycle Proteins
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • beta Catenin
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I