The EGF receptor family comprises several related receptor tyrosine kinases that are frequently overexpressed in a variety of carcinomas. Members of this receptor family include EGFR (HER1), Neu (ErbB-2, HER2), ErbB-3 (HER3) and ErbB-4 (HER4), which form either homodimers or heterodimers upon ligand binding. Neu, a glycoprotein, undergoes transactivation upon heterodimerization with other EGF receptor family members. Neu heterodimerization with ErbB-3 recruits heregulin, which induces phosphoinositide (PI) 3-kinase activation. Activation of Neu potentiates tumor cell motility and protease secretion and invasion, and also modulates cell cycle checkpoint function, DNA repair and apoptotic responses. Amplification and/or overexpression of Neu occurs in 20-30% of breast carcinomas. Measurement of increased Neu expression can be a predictor of disease prognosis. Neu may also prove to be a promising target for therapeutic agents.
