Structure of HER receptors and intracellular localisation of downstream effector elements gives insight into mechanism of tumour growth promotion

Excerpt

Since the discovery that the receptor HER2 (erbB2/neu) was overexpressed in 20–30% of breast cancers, and its subsequent association with poor prognosis, there has been much interest in this protein. The production of the humanised antibody to HER2 (Herceptin [trastuzumab]) and the use of Herceptin to treat patients with HER2 positive tumours has emphasised the potential of targeted treatments for breast cancer. The differences between HER2 and the other members of the type I receptor family (epidermal growth factor receptor [EGFR], HER3, HER4) have also been researched. HER2 differs in that it has no known ligand and when overexpressed HER2 can form dimers. In contrast the other receptors have several known ligands that promote dimer formation on binding. HER receptors can form both homo and heterodimers with HER2 acting as the preferred dimer partner. The activation of these receptors either by overexpression or ligand binding leads to the activation of intracellular growth promoting pathways and thus promotes tumour growth. …