The HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor and a member of the epidermal growth factor receptors (EGFR/ErbB) family. Over-expression of this oncogene is known to contribute to pathogenesis and aggressive progression in breast cancer. On the other hand, angiogenesis is a physiological process of forming new blood vessels from pre-existing ones; however it is essential for tumor growth and transitional from benign stage to malignant form and also fundamental process for metastasis of tumors. In this study the main aim was to investigate whether angiogenesis is the cause for increased aggressive behavior of HER2 overexpression subtype in breast cancer. A variety of approaches were employed to investigate the main aim: quantification of angiogenesis using a mouse cancer cells implanted model; Drabkin’s assay for hemoglobin measurement; morphology assessment of cell lines; Bio-Plex analysis of angiogenesis factors angiopoietin-2, follistatin, G-CSF, HGF, IL-8, Leptin, PDGF-BB, PECAM-1 and VEGF; and reverse transcriptase-PCR on VEGFA and HIF-1 alpha genes expression. The data from this study showed that the AU-565 cell line which over-expresses HER2 receptors showed a significant decrease in both tumor weight and hemoglobin measurement when the cells were treated with anti-HER2 implanted in nude mice. Also, the data showed an increased expression of angiogenic factors and genes (mainly VEGF, VEGFA, Angiopoietin, and IL-8) in AU-565 as compared to MCF-7 cells, which have low expression of HER2 receptors. This suggests that breast cancer with HER2/neuoncogenes is associated with more angiogenic activities that result in an increased aggressive behavior of this form of cancer
