ERBB2 and neoplasm: Reduction of HER2 activity or expression leads to down-regulation of Akt and ERK1/2 signaling and, consequently, represses the expression of angiopoietin-2, an initial factor required for tumor angiogenesis, indicating that HER2 mediates tumor angiogenesis and metastasis by up-regulation of angiopoietin-2 expression [7].