Both clinical and laboratory data indicated that overexpression of HER2 / ERBB2 contributes to increased metastatic potential of cancer cells. Studies in node- positive breast cancer patients revealed a correlation between the number of lymph node metastases and HER2 / ERBB2 overexpression. Experiments using transgenic mice showed that introduction of the HER2 / ERBB2 gene into mice can induce mammary tumors and metastases in mice. Consistent with these observations, we found that expression of activated rat neu oncogene in 3T3 cells is su?ffcient to induce experimental metastasis in nude mice. Later, we demonstrated that overexpression of p185 HER2 / ERBB2 could enhance the metastatic potential of human breast and lung cancer cells by experimental metastasis assays on a panel of breast cancer transfectants and lung cancer transfectants expressing di?fferent levels of p185HER2 / ERBB2. In addition, we and others have shown that: (1) HER2 / ERBB2 overexpression can upregulate MMP-9 and MMP-2 protease activities and increase the invasiveness of breast cancer cells; (2) HER2 / ERBB2 overexpression can increase VEGF expression in breast cancer cells, which, together with higher MMP-9 activity, may lead to stronger angiogenic response; (3) HER2 / ERBB2 overexpression can confer apoptosis resistance (survival advantage) in breast cancer cells. Together, upregulation of MMPs and angio- genesis as well as apoptosis resistance can contribute to increased metastatic potential.
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