Selection of monoclonal antibodies which induce internalization and phosphorylation of p185(HER2) and growth inhibition of cells with HER2/neu gene amplification

E. Tagliabue, F. Centis, M. Campiglio, A. Mastroianni, S. Martignone, R. Pellegrini, P. C. Casalini Lanzi, S. Menard, M. I. Colnaghi

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Abstract

In order to obtain further information on the biological role of the HER2/neu oncoprotein monoclonal antibodies (MAbs) were produced against the p185 extracellular domain. To immunize the mice and screen the hybridoma supernatants we selected a lung adenocarcinoma cell line (Calu-3), which demonstrated an over-expression of p185(HER2) measured as the reactivity with polyclonal rabbit serum to the 14-amino-acid carboxy-terminal-HER2/neu. Two MAbs, designated MGR2 (IgG1) and MGR3 (IgG2), selected for reactivity on Calu-3 and negativity on A431 live cells, the reference target cell for EGF receptor expression, were found to immunoprecipitate a 185-kDa molecule. Immunodepletion experiments with the polyclonal antiserum and cross-competition experiments indicated that the 2 reagents recognized 2 different epitopes located on the p185(HER2) molecule. One of the 2 MAbs, MGR3 was found to internalize, induce p185(HER2) phosphorylation and inhibit tumor cell growth in vitro. These results indicate that MGR3 is directed against a determinant located in the p185(HER2) ligand binding site and may compete with the p185(HER2) ligand, but is incapable of inducing a complete mitotic signal.

Original languageEnglish
Pages (from-to)933-937
Number of pages5
JournalInternational Journal of Cancer
Volume47
Issue number6
Publication statusPublished - 1991

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Tagliabue, E., Centis, F., Campiglio, M., Mastroianni, A., Martignone, S., Pellegrini, R., Casalini Lanzi, P. C., Menard, S., & Colnaghi, M. I. (1991). Selection of monoclonal antibodies which induce internalization and phosphorylation of p185(HER2) and growth inhibition of cells with HER2/neu gene amplification. International Journal of Cancer, 47(6), 933-937.