Protein kinase C regulates bombesin-induced rapid VEGF secretion in neuroblastoma cells

Cameron Schlegel, Pritha Paul, Sora Lee, Kwang Woon Kim, Nadja Colon, Jingbo Qiao, Dai H. Chung

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: Intracellular signaling responsible for gastrin-releasing peptide (GRP) receptor-mediated neovascularization is not clearly understood. We sought to determine the cellular mechanisms involved in the GRP receptor regulation of vascular endothelial growth factor (VEGF) release in neuroblastoma cells. Materials and Methods: BE(2)-C cells were treated with bombesin (BBS), the amphibian equivalent of GRP, Phorbol myristate acetate (PMA) a PKC agonist, or GF109293X (GFX), and analyses were performed for VEGF secretion, phosphorylated protein kinase B (AKT), extracellular signal-regulated kinases (ERK) and protein kinase D (PKD) expression. Results: BBS rapidly increased VEGF secretion at 30 min. Pre-treatment with PMA alone produced similar results; this effect was synergistic with the addition of GRP. Conversely, GFX blocked PMA-stimulated increase in VEGF secretion. Immunofluorescent staining for VEGF correlated to BBS, PMA and GFX. Conclusion: PKC is critically responsible for rapid VEGF secretion by GRP receptor signaling in neuroblastoma cells. Inhibition of VEGF significantly reduced GRP-mediated cell proliferation, suggesting its crucial role in neuroblastoma tumorigenesis.

Original languageEnglish (US)
Pages (from-to)4691-4696
Number of pages6
JournalAnticancer Research
Volume32
Issue number11
StatePublished - Nov 1 2012

    Fingerprint

Keywords

  • BBS
  • GRP
  • Neuroblastoma
  • PKC
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this