Ets transcriptional regulation of gastrin-releasing peptide receptor in neuroblastomas

Jingbo Qiao, Jeremy Cree, Junghee Kang, Sunghoon Kim, B. Mark Evers, Dai H. Chung

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background We have demonstrated that gastrin-releasing peptide (GRP) binds specifically to its cell surface receptor, GRP-R, to act as an autocrine/paracrine growth factor for neuroblastomas (NBs); an increased expression of GRP-R was found in more advanced-stage NBs. Ets family proteins are nuclear targets for intracellular kinase pathways that can lead to cell proliferation; however, a potential role of Ets in the expression of GRP-R in NBs is unknown. Therefore, the purpose of our study was to determine whether Ets regulates transcriptional activity of GRP-R in NBs. Methods We identified multiple DNA-binding sites for various nuclear transcription factors in the proximal (ie, 263 bp) GRP-R promoter. Luciferase assay was performed to measure GRP-R promoter activity that contained site-specific mutations of various binding elements. Electrophoretic mobility shift assay was performed to determine transcription factor-binding activity. Results Mutation of a consensus Ets-binding site in the GRP-R promoter significantly decreased GRP-R promoter activity. Electrophoretic mobility shift assay demonstrated a decrease in Ets nuclear protein-binding activity. Furthermore, overexpression of Ets1 resulted in upregulation of GRP-R promoter activity. Conclusions Our results demonstrate that Ets is a transcription factor that significantly contributes to the GRP-R transcription in NBs. This finding may allow us to develop novel molecular tools to downregulate expression of GRP-R and hence inhibit mitogenic effects of GRP in NBs.

Original languageEnglish (US)
Pages (from-to)489-494
Number of pages6
JournalSurgery
Volume136
Issue number2
DOIs
StatePublished - Aug 2004
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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