Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies

@article{Drebin1985DownmodulationOA,
  title={Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies},
  author={Jeffrey Adam Drebin and Victoria C. Link and David F. Stern and Robert A. Weinberg and Mark Irwin Greene},
  journal={Cell},
  year={1985},
  volume={41},
  pages={695-706}
}
Demonstration by two-color flow cytometry that tyrosine kinase activity is required for down-modulation of the oncogenic neu receptor.
TLDR
It is found that fibroblasts expressing the tyrosine kinase-defective mutants cannot form foci in culture, colonies in soft agar, or tumors in immunocompromised mice, which strongly suggest that the fate of the neu receptor, once internalized, is directed by its tyrosin kinase activity.
The role of non-ras transforming genes in chemical carcinogenesis.
  • C. Cooper
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    Environmental health perspectives
  • 1991
DNA transfection experiments using the NIH 3T3 mouse fibroblast cell line have demonstrated that chemically induced tumors and chemically transformed cell lines frequently contain dominant
Oncogene-mediated Multistep Transformation of C 3 H 10 T 1 / 2 Cells 1
TLDR
The studies demonstrate that the mouse embryonic cell line is an exception and provides a model system in which partially transformed phenotypes, in a progression toward malignant transforma tion, can be isolated and studied and is potentiated by the presence of a functional gag-myc protein.
p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity
TLDR
The normal form of p185 was structurally similar to its transforming counterpart, indicating that activation of the neu oncogene did not cause major structural alterations in the gene product, and supporting the idea that normal p185 functions as a growth factor receptor.
Biological studies and potential therapeutic applications of monoclonal antibodies and small molecules reactive with theneu/c-erbB-2 protein
TLDR
The laboratory has demonstrated a direct effect of anti-p185neu/c-erbB-2 antibodies which requires receptor ligation and is exploiting the direct efficacy of this monoclonal antibody by developing small molecules (peptides and organic mimietics) based on anti-magnifying antibody structure that can mediate similar receptor binding and biological effects.
Interaction of the neu/p185 and EGF receptor tyrosine kinases: Implications for cellular transformation and tumor therapy
TLDR
The physical and functional interaction of p185c‐neu and EGFR leads to the formation of a highly active, heterodimeric tyrosine kinase complex which synergistically activates cellular transformation.
Growth inhibition by dominant‐negative mutations of the NEU‐encoded oncoprotein
TLDR
Kinase‐deficient mutants of the neu gene exert a dominant‐negative effect on phosphorylation of receptor complexes, resulting in a reversion of the transformed phenotype.
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