Angiogenetic axis angiopoietins/Tie2 and VEGF in familial breast cancer

Eur J Hum Genet. 2013 Aug;21(8):824-30. doi: 10.1038/ejhg.2012.273. Epub 2012 Dec 12.

Abstract

Angiogenesis leads to the formation of blood vessels from pre-existing ones, allowing tumor growth. Vascular endothelial growth factor (VEGF) and Angiopoietins (Ang-1, Ang-2) have a pivotal role in tumor angiogenesis but few data regarding their role in hereditary breast cancer are available. The aim of the present study was to analyze Ang-1, Ang-2, tyrosine-protein kinase receptor Tie2 and VEGF expression and their correlation in a cohort of familial and sporadic breast cancers in order to verify whether the presence of germline mutations in BRCA may have a role in tumor microenvironment regulation. Tumor samples from a cohort of 41 patients with a first diagnosis and a family history of breast cancer and 19 patients with sporadic breast cancers were enrolled. The expression of Tie2, Ang-1, Ang-2 and VEGF were analyzed by quantitative real-time PCR. Patients harboring BRCA mutations had higher levels of Ang-1 (P=0.05), Ang-2 (P=0.02) and VEGF (P=0.04) mRNA compared with those without BRCA mutations (BRCAX). The same was observed in triple-negative breast cancer (TNBC). Moreover, a positive correlation between Ang-2 and VEGF was found in both the familial breast cancer group (BRCA carriers: r=0.83; P<0.0001 and BRCAX: r=0.58; P=0.008) and in TNBC (r=0.62; P=0.007). The higher levels of Ang-1, Ang-2 and VEGF mRNA found in BRCA carriers and TNBCs suggest that they could be attractive angiogenic therapeutic targets in these breast cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiopoietin-1 / genetics*
  • Angiopoietin-2 / genetics*
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cohort Studies
  • Family Health
  • Female
  • Gene Expression Regulation, Neoplastic
  • Germ-Line Mutation
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Receptor, ErbB-2 / metabolism
  • Receptor, TIE-2 / genetics*
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Angiopoietin-1
  • Angiopoietin-2
  • BRCA1 Protein
  • BRCA2 Protein
  • BRCA2 protein, human
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Vascular Endothelial Growth Factor A
  • Receptor, ErbB-2
  • Receptor, TIE-2