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Vasoactive intestinal peptide (VIP) increases vascular endothelial growth factor (VEGF) expression and secretion in human breast cancer cells.

Abstract
Previous studies have shown that vasoactive intestinal peptide (VIP) and its receptors (VPAC(1) and VPAC(2) receptors) are involved in promotion and growth of many human tumours including breast cancer. Here we investigated whether VIP regulates the expression of the main angiogenic factor, vascular endothelial cell growth factor (VEGF) in human oestrogen-dependent (T47D) and oestrogen-independent (MDA-MB-4687) breast cancer cells. Semiquantitative and quantitative real-time RT-PCRs were used at mRNA level whereas enzyme immunoanalysis was performed at protein level. Both cancer cell lines expressed VIP and VPAC(1) (but not VPAC(2)) receptors that were functional as shown by VIP stimulation of adenylate cyclase activity. VIP induced VEGF expression at both mRNA and protein levels following a time-dependent pattern. The responses were faster in T47D than in MDA-MB-468 cells. The observed VIP regulation of VEGF expression appears to be modulated at least by the cAMP/protein kinase A (PKA) and the phosphoinositide 3-kinase (PI3-K) signalling systems as shown by studies of adenylate cyclase stimulation and using specific kinase inhibitors such as H89 and wortmannin. These actions suggest a proangiogenic potential of VIP in breast cancer.
AuthorsAna Valdehita, María J Carmena, Beatriz Collado, Juan C Prieto, Ana M Bajo
JournalRegulatory peptides (Regul Pept) Vol. 144 Issue 1-3 Pg. 101-8 (Dec 04 2007) ISSN: 0167-0115 [Print] Netherlands
PMID17683807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vasoactive Intestinal Peptide
  • Cyclic AMP
  • Phosphatidylinositol 3-Kinases
  • Cyclic AMP-Dependent Protein Kinases
Topics
  • Breast Neoplasms (genetics, metabolism)
  • Cell Line, Tumor
  • Cyclic AMP (metabolism)
  • Cyclic AMP-Dependent Protein Kinases (metabolism)
  • Female
  • Gene Expression
  • Humans
  • Phosphatidylinositol 3-Kinases (metabolism)
  • RNA, Messenger (metabolism)
  • Signal Transduction
  • Vascular Endothelial Growth Factor A (genetics, metabolism)
  • Vasoactive Intestinal Peptide (genetics, metabolism)

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