Interaction between erbB-receptors and heregulin in breast cancer tumor progression and drug resistance.

The type I growth factor receptor family is increasingly recognized as important in the development and maintenance of breast cancer. The family currently consists of four closely related members: the epidermal growth factor receptor (EGF-R/erbB-1), erbB-2, erbB-3 and erbB-4. Putative ligands which bind directly to or indirectly activate erbB-2/3/4 have been characterized recently. This still growing family of EGF-related growth factors includes gp30, its homolog heregulin (HRG), the rat homolog neu differentiation factor (NDF), glial growth factors (GLIA), ARIA and a 50 kDa factor from COLO 16 cells. The understanding of the function, biology and interactions of these growth factor receptors and their ligands will have far-reaching implications for the prognosis and treatment of breast cancer. This review focuses on advances and future directions for further investigations intended to clarify the mechanism and significance of erbB/ligand interactions in breast cancer.