ERBB RECEPTOR ACTIVATION, CELL MORPHOLOGY CHANGES, AND APOPTOSIS INDUCED BY ANTI-HER2 MONOCLONAL-ANTIBODIES

A panel of mAbs were generated against the purified soluble form of er bB2/Her2 receptor, corresponding to the extracellular region of the re ceptor, and examined for their ability to mimic the receptor ligand. S ome of the mAbs strongly induced tyrosine phosphorylation of 180-185 k Da proteins, including not only Her2 but also Her3 and Her4 receptors, when they were expressed on the surface of breast cancer cells. These mAbs do not cross-react with Her3 or Her4 as demonstrated by competit ion study. Receptor phosphorylation was also observed with the cell li nes transfected with Her2 or a chimeric receptor consisting of the ext racellular domain of Her2 and the transmembrane and cytoplasmic domain s of epidermal growth factor receptor. Selected mAbs were tested for t heir ability to change cell morphology, and one specific mAb, mAb74, i nduced cell morphology changes and apoptosis. (C) 1996 Academic Press, Inc.