title: Angiogenetic axis angiopoietins/Tie2 and VEGF in familial breast cancer.
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.
authors.affiliation: Molecular Genetic Laboratory, National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Bari, Italy.
authors.forename: K
authors.initials: K
authors.lastname: Danza
authors.forename: B
authors.initials: B
authors.lastname: Pilato
authors.forename: R
authors.initials: R
authors.lastname: Lacalamita
authors.forename: T
authors.initials: T
authors.lastname: Addati
authors.forename: F
authors.initials: F
authors.lastname: Giotta
authors.forename: A
authors.initials: A
authors.lastname: Bruno
authors.forename: A
authors.initials: A
authors.lastname: Paradiso
authors.forename: S
authors.initials: S
authors.lastname: Tommasi
mesh_terms: D000328:Adult; D042683:Angiopoietin-1 / Q000235:genetics*; D042702:Angiopoietin-2 / Q000235:genetics*; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D005192:Family Health; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018095:Germ-Line Mutation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000235:genetics*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; D042787:Receptor, TIE-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D042461:Vascular Endothelial Growth Factor A; C551750:BRCA2 protein, human