ErbB2 overexpression in mammary cells upregulates VEGF through the core promoter

Robyn M.B. Loureiro, Arindel S.R. Maharaj, David Dankort, William J. Muller, Patricia A. D'Amore

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

The angiogenic molecule, vascular endothelial growth factor (VEGF), is a critical regulator of normal and pathologic angiogenesis. ErbB2, an epidermal growth factor receptor family member whose overexpression in mammary tumors is correlated with poor patient prognosis, has been implicated as a positive modulator of VEGF expression. Mammary tumor cells overexpressing ErbB2 (NAFA cells) and a normal mouse mammary cell line (HC11) transfected with ErbB2 expression vectors were used to study the effects of ErbB2 overexpression on VEGF regulation. We found that ErbB2 overexpression led to an increase in endogenous VEGF mRNA as well as ErbB3 protein levels in HC11 cells. Additionally, we determined that ErbB2 overexpression-mediated upregulation of VEGF involves at least two distinct promoter elements, one previously identified as the hypoxia responsive element and the other the core promoter region (-161 to -51 bp), which is specifically controlled via two adjacent SP1 binding sites (-80 to -60 bp).

Original languageEnglish (US)
Pages (from-to)455-465
Number of pages11
JournalBiochemical and biophysical research communications
Volume326
Issue number2
DOIs
StatePublished - Jan 14 2005
Externally publishedYes

Keywords

  • Angiogenesis
  • Core promoter
  • ErbB2
  • Mammary cells
  • SP1
  • Transcriptional regulation
  • VEGF

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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