Expression of the erbB-2 family of growth factor receptors and their ligands in breast cancers. Implication for tumor biology and clinical behavior.

Transmembrane receptor tyrosine kinases that bind to growth factors transmit signals that are essential to growth and differentiation. These receptors can be classified into groups based on their structure. One group implicated in the pathogenesis of breast cancer contains receptors belonging to the erbB family. This group includes the epidermal growth factor receptors, the HER-2/neu (erbB-2), HER-3, and HER-4. Despite the structural similarity of these receptors, HER-2/neu, HER-4, and HER-3 do not bind to any ligand of the epidermal growth factor receptor. However, a 44-kD glycoprotein called neu differentiation factor (neu differentiation factor/heregulin) has been isolated. This ligand phosphorylates the HER-2/neu receptor and binds directly to HER-4 and HER-3. The abundance of erbB receptors and their ligands in breast cancers points to their functional importance in the pathogenesis and biological behavior of breast cancers. Furthermore, these receptors and ligands may hold a promise for targeted therapy for breast cancer in the future.