Prolactin-induced expression of vascular endothelial growth factor via Egr-1

Anita S. Goldhar, Barbara K. Vonderhaar, Josephine F. Trott, Russell C. Hovey

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Angiogenesis is a dynamic process regulated by both local and systemic factors. Among these is vascular endothelial growth factor (VEGF), a potent effector of angiogenesis and vascular permeability. Previously we showed that VEGF is temporally and spatially regulated in the mouse mammary gland during development and lactation. Given the functions of prolactin (PRL) during these stages and the supporting role of the vasculature, we investigated the regulation of VEGF by PRL. Treatment of HC11 mouse mammary epithelial and Nb2 rat lymphoma cells with PRL induced VEGF expression. Deletion and mutation analysis identified a GC-rich region in the proximal region of the VEGF promoter that constitutively bound Sp1 and PRL-induced Egr-1. These sites conferred PRL-responsiveness leading to increased VEGF transcription. The induction of VEGF by PRL was PRL receptor-, Jak2- and MAP kinase kinase-dependent. Our results indicate that PRL induces VEGF expression through Egr-1, and implicates VEGF as an intermediary of PRL-regulated angiogenesis.

Original languageEnglish (US)
Pages (from-to)9-19
Number of pages11
JournalMolecular and Cellular Endocrinology
Volume232
Issue number1-2
DOIs
StatePublished - Mar 31 2005
Externally publishedYes

Keywords

  • Angiogenesis
  • Lymphoma
  • Mammary gland
  • Prolactin

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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