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.
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Acknowledgements
We thank Caroline Oakley for manuscript revision. The study was partially funded by Progetto Strategico Regionale Puglia – APQ ‘The biotechnologies for the targeted therapy in oncology (Biotecnoter)’ and by Progetto regionale Puglia (DIEF 2007).
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Danza, K., Pilato, B., Lacalamita, R. et al. Angiogenetic axis angiopoietins/Tie2 and VEGF in familial breast cancer. Eur J Hum Genet 21, 824–830 (2013). https://doi.org/10.1038/ejhg.2012.273
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DOI: https://doi.org/10.1038/ejhg.2012.273
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