June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
The PDGF-PDGFR Signaling Pathway Regulates AKT Cell Survival and NF-kB anti-apoptotic effects in Retinoblastoma
Author Affiliations & Notes
  • Matthew W Wilson
    Ophthal/Hamilton Eye Int, Univ of Tennessee Health Sci Ctr, Memphis, Tennessee, United States
    Surgery and Pathology, St Jude Children's Research Hospital, Memphis, Tennessee, United States
  • Zachary K. Goldsmith
    Ophthal/Hamilton Eye Int, Univ of Tennessee Health Sci Ctr, Memphis, Tennessee, United States
  • William Coppess
    Ophthal/Hamilton Eye Int, Univ of Tennessee Health Sci Ctr, Memphis, Tennessee, United States
  • Kelley Yuan
    Ophthal/Hamilton Eye Int, Univ of Tennessee Health Sci Ctr, Memphis, Tennessee, United States
  • Madison Ritter
    Ophthal/Hamilton Eye Int, Univ of Tennessee Health Sci Ctr, Memphis, Tennessee, United States
  • Andrew Irvine
    Ophthal/Hamilton Eye Int, Univ of Tennessee Health Sci Ctr, Memphis, Tennessee, United States
  • Rachel Brennan
    Oncology, St Jude Children's Research Hospital, Memphis, Tennessee, United States
  • Vanessa Marie Morales
    Ophthal/Hamilton Eye Int, Univ of Tennessee Health Sci Ctr, Memphis, Tennessee, United States
    Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Footnotes
    Commercial Relationships   Matthew Wilson, None; Zachary Goldsmith, None; William Coppess, None; Kelley Yuan, None; Madison Ritter, None; Andrew Irvine, None; Rachel Brennan, None; Vanessa Morales, None
  • Footnotes
    Support  Research to Prevent Blindness, Inc and St Jude Children's Research Hospital Endowed Chair in Pediatric Ophthalmology
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1778. doi:
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    • Get Citation

      Matthew W Wilson, Zachary K. Goldsmith, William Coppess, Kelley Yuan, Madison Ritter, Andrew Irvine, Rachel Brennan, Vanessa Marie Morales; The PDGF-PDGFR Signaling Pathway Regulates AKT Cell Survival and NF-kB anti-apoptotic effects in Retinoblastoma
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):1778.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Purpose: Vitreous seeding remains the greatest challenge in treatment of retinoblastoma (Rb). In part due to poor understanding of the interactions between Rb and vitreous microenvironment. Previously, we identified the PDGF-PDGFR signaling as a signaling pathway that sustains angiogenesis in both an autocrine and paracrine fashion. Here, we investigated how the PDGF-PDGFR signaling pathway regulates cell proliferation and cell survival in Rb.

Methods : Methods: We performed in vitro cell culture assays of Y79 Rb cells, considered the metastatic model of the disease. Cells were cultured in different conditions, which include stimulatory (recombinant human PDGF) and inhibitory (imatinib mesylate) conditions of the PDGF-PDGFR signaling pathway. Assessment of cell survival included measurement of members of the AKT signaling pathway and protein levels of the anti-apoptotic molecule BCL-2 by Western blot analyses. Nuclear translocation of the p65 subunit of NF-kB was measured by imaging flow cytometry using FlowSight®.

Results : Results: Our results suggest that PDGF-PDGFR signaling regulates Rb cell survival through AKT. Additionally, we found a significant reduction in BCL-2, concomitant with an increase in caspase-3 activity. We also found a significant decrease in the nuclear translocation of the p65 subunit of NF-kB

Conclusions : Conclusions: The outcomes of this study reveal that PDGF-PDGFR signaling regulates cell survival in addition to the previously described sustainment of angiogenesis. We found PDGF-PDGFR signaling is involved in the activation of the AKT survival pathway. Inhibition of PDGF-PDFGR signaling decreases NF-kB nuclear translocation, ultimately resulting in increased susceptibility to apoptosis.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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