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.
|Number of pages||5|
|Journal||International Journal of Cancer|
|Publication status||Published - 1991|
ASJC Scopus subject areas
- Cancer Research