"Additionally, AFM was also applied to investigate the effect of Trastuzumab, as well as Pertuzumab, on HER2-modulated EGF-EGFR interactions, which demonstrated that EGF bound to EGFR more stably in the cells co-expressing EGFR and HER2, and the binding enhancement in the presence of HER2 was inhibited by either Trastuzumab or Pertuzumab [ xref ]."
"For example, binding of two monomeric ErbB2 proteins to an EGF-induced homodimer of EGFR may cause homodimerization of the ErbB2 molecules followed by their trans-autophosphorylation and consequent ac[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
"In this manuscript we demonstrate through combination of scattering spectroscopy, electron microscopy, and generalized multiple particle Mie theory (GMT) simulations that the density- and morphology-dependent spectral response of Au nanoparticle (NP) immunolabels bound to the epidermal growth factor receptors ErbB1 and ErbB2 encodes quantitative information of both the cell surface expression and spatial clustering of the two receptors in different unliganded in vitro cancer cell lines (SKBR3, MCF7, A431)."
"It is assumed that the mechanism of transactivation
involves epidermal growth factor binding to EGFR, followed by
transphosphorylation of ErbB2 by the active EGFR kinase."
"Living-cell single-molecule force spectroscopy (SMFS) combined by Atomic Force Microscopy (AFM) was used by this team of scientists to investigate the effect of two monoclonal antibodies used in cancer therapy, Trastuzumab and Pertuzumab, on HER2-modulated EGF-EGFR interaction, demonstrating the utility of this technique in characterizing the effects of protein-based therapeutics on membrane receptors."
"Thus, it is possible that two ErbB2 proteins could bind to an EGF-induced homodimer of EGFR resulting in their homodimerization, autophosphorylation and subsequent activation ."
"Results from co-immunoprecipitation experiments and western blot analyses indicate that tyrosine-phosphorylated ErbB2 and EGFR monomers and stable ErbB2/EGFR high molecular complexes (heterodimers) are formed following EGF stimulation, even if the receptors co-immunoprecipitates also in the absence of the ligand; these data suggest the existence of pre-dimerization inactive receptor clusters on the cell surface."
"EGF predominantly binds EGFR to induce both EGFR homodimers and EGFR–HER2 heterodimers, whereas HRG predominantly binds HER3 and HER4, inducing HER2–HER3 and HER2–HER4 heterodimers."
"Col IV, LM and FN (but not Col I) adhesion reduce EGF binding to its receptors, EGFR and ErbB2 ( xref )."
"Exposure of 2 or 20 ug/mL 2C4, a HER2 monoclonal antibody which inhibits HER2-HER3 heterodimerization [ xref ], decreased EGF-dependent HER1-HER2 heterodimer formation with a small concomitant increase in HER1-HER1 homodimerization (Figure xref )."
"In this work, we have applied living-cell single-molecule force spectroscopy (SMFS) by Atomic Force Microscopy (AFM) to investigate the effect of Trastuzumab, as well as Pertuzumab, on HER2-modulated EGF-EGFR interaction."
"The formation of EGF-dependent HER1-HER2 heterodimers were inhibited by the HER2-targeted monoclonal antibody 2C4 and stabilized by the HER1 tyrosine kinase inhibitor (TKI) erlotinib."
"Here, we have generated six such bispecific targeting proteins, each comprising two monomeric affibody molecules with specific binding to either of the two human epidermal growth factor receptors, EGFR and HER2, respectively."
"In our own solution biophysical studies, we observed weak heterodimerization of ErbB2 with the neuregulin-bound extracellular regions of ErbB3 or ErbB4 [ xref ], but failed to detect EGF-induced association of the EGFR and ErbB2 extracellular regions (or other anticipated heterodimers)."
"The monoclonal antibodies cetuximab and trastuzumab, which bind to the epidermal growth factor receptors EGFR and HER-2, respectively, were chosen because they are already established targeting vectors to deliver radioactive isotopes and fluorescent dyes separately. xref - xref EGFR and HER2 are expressed/over-expressed in a variety of cancer cell lines."