Ets1 transcription factor mediates gastrin-releasing peptide-induced IL-8 regulation in neuroblastoma cells

Jingbo Qiao, Jung Hee Kang, Jeremy Cree, B. Mark Evers, Dai H. Chung

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Angiogenesis plays a critical role in tumor progression in various cancers, including neuroblastoma. We have previously shown that gastrin-releasing peptide (GRP) stimulates neuroblastoma growth and that its cell surface receptors, gastrin-releasing peptide receptors (GRP-R), are overexpressed in advanced-stage human neuroblastomas; however, the effects of GRP on angiogenesis are not clearly elucidated. Interleukin (IL) 8, a proinflammatory chemokine, plays an important role during tumor angiogenesis. Ets transcription factors, such as oncoproteins, cause tumor development and are also known to induce IL-8 expression. In the present study, we found an increased expression of Ets1 in more undifferentiated human neuroblastomas. Stable transfection of SK-N-SH human neuroblastoma cells with Ets1 plasmid resulted in increased IL-8 luciferase activity and IL-8 secretion into cell culture media. Conversely, silencing of Ets1 resulted in a significant decrease in IL-8 secretion in SK-N-SH cells. Moreover, exogenous GRP treatment increased Ets1 (T38) phosphorylation and Ets1 nuclear accumulation, and enhanced Ets1 binding to its DNA consensus sequence, resulting in the stimulation of IL-8 mRNA expression and protein secretion. Our findings demonstrate that GRP upregulates proangiogenic IL-8 expression in an Ets1-dependent manner, suggesting a critical role of this process during GRP-induced neuroblastoma angiogenesis and metastasis.

Original languageEnglish (US)
Pages (from-to)184-191
Number of pages8
JournalNeoplasia
Volume9
Issue number3
DOIs
StatePublished - Mar 2007

Keywords

  • Angiogenesis
  • Ets1
  • GRP
  • IL-8
  • Neuroblastoma

ASJC Scopus subject areas

  • Cancer Research

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