title: Antibody-induced inhibition of growth of egfr overexpressing tumors occurs in the absence of receptor down-regulation.
abstract: Using two antibodies which bind to distinct epitopes on the extracellular domain of the EGF receptor (EGFR) we have developed a novel method for monitoring EGFR expression and the behaviour of monoclonal antibody (mAb) bound to the receptor. We have used this method to investigate the fate of the rat mAb ICR80 following binding to the EGF receptor on tumour cells. Antibody ICR80, which was raised against the external domain of the EGF receptor on a human brain tumour (A172) cell line and was employed in this study, has the following properties. It (a) blocks the binding of EGF, TGF alpha and HB-EGF to the EGFR, (b) prevents the EGF, TGF alpha and HB-EGF induced tyrosine phosphorylation of the EGFR, and (c) inhibits the growth in vitro of the head and neck tumour (HN5) cell line overexpressing the EGF receptor. Our results presented herein also show that EGF receptor blockade by antibody ICR80 is not accompanied by detectable loss of antibody from the cell surface or down-regulation of the receptor. On the basis of these results we conclude that the long-lasting blockade of the EGF receptor on tumour cells by antibody may be an important factor in preventing the binding of growth factors which are essential for their continued proliferation.
authors.forename: H
authors.initials: H
authors.lastname: Modjtahedi
authors.forename: C
authors.initials: C
authors.lastname: Dean