Human epidermal growth factor receptor-2 (HER2/erbB-2) belongs to a family of 
four transmembrane receptors involved in signal transduction pathways that 
regulate cell growth and differentiation. Overexpression/amplification of HER2 
is associated with malignancy and a poor prognosis in breast cancer. HER2 acts 
as a networking receptor that mediates signaling to cancer cells, causing them 
to proliferate. HER receptors exist as monomers but dimerize on ligand binding. 
HER ligands are bivalent growth factor molecules whose low-affinity site binds 
to HER2. No HER2-specific ligand has been identified but HER2 is the preferred 
heterodimerization partner for other HER receptors. HER2-containing heterodimers 
are relatively long-lived and potent. HER3 has no inherent activity and is the 
major and most potent dimerization partner of HER2. HER2 overexpression biases 
the formation of HER2-containing heterodimers, leading to enhanced 
responsiveness to stromal growth factors and oncogenic transformation. Removal 
of HER2 from the cell surface or inhibition of its intrinsic enzymatic activity 
may reduce oncogenicity. Our research suggests that the antitumor efficacy of 
HER2-specific antibodies such as Herceptin relates to their ability to direct 
HER2 to a Cbl- dependent endocytosis and degradation pathway. The reported 
clinical therapeutic efficacy of anti-HER2 monoclonal antibodies in breast 
cancer highlights the importance of understanding the biology of HER2.