EXPRESSION OF THE ERBB-2 FAMILY OF GROWTH-FACTOR RECEPTORS AND THEIR LIGANDS IN BREAST CANCERS - IMPLICATION FOR TUMOR BIOLOGY AND CLINICALBEHAVIOR

Transmembrane receptor tyrosine kinases that bind to growth factors tr ansmit 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 recept ors belonging to the erbB family. This group includes the epidermal gr owth factor receptors, the HER-2/neu (erbB-2), HER-3, and HER-4. Despi te 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 recept or. However, a 44-kD glycoprotein called neu differentiation factor (n eu differentiation factor/heregulin) has been isolated. This ligand ph osphorylates the HER-2/neu receptor and binds directly to HER-4 and HE R-3. The abundance of erbB receptors and their ligands in breast cance rs points to their functional importance in the pathogenesis and biolo gical behavior of breast cancers. Furthermore, these receptors and lig ands may hold a promise for targeted therapy for breast cancer in the future.