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

  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},
Demonstration by two-color flow cytometry that tyrosine kinase activity is required for down-modulation of the oncogenic neu receptor.
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
  • Biology
    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
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
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
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
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
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.


Monoclonal antibodies to the p21 products of the transforming gene of Harvey murine sarcoma virus and of the cellular ras gene family
Eight rat lymphocyte-myeloma hybrid cell lines producing monoclonal antibodies that react with the 21,000-dalton transforming protein (p21) encoded by the v-ras gene of Harvey murine sarcoma virus are isolated, suggesting that an endogenous gene closely related to Kirsten-ras is expressed in these cells.
Fibroblast immortality is a prerequisite for transformation by EJ c-Ha-ras oncogene
It is shown that EJ c-Ha-ras-1 lacks complete transforming activity when transfected into normal fibroblasts which have a limited life-span, but can fully transform fibro Blasts that have been newly ‘immortalized’ by carcinogens.
A novel transforming gene in a human malignant melanoma cell line
The presence of transforming activity in the DNA from a human melanoma cell line which shows weak homology with members of the ras oncogene family is described.
Flat revertants isolated from Kirsten sarcoma virus-transformed cells are resistant to the action of specific oncogenes.
Two flat revertants have been isolated from mutagen-treated populations of Kirsten murine sarcoma virus (Ki-MuSV)-transformed NIH/3T3 cells, and analysis of hybrid cells resulting from the fusion of these revertants to cell lines transformed by other retroviruses showed that the action of certain oncogenes structurally unrelated to v-ki-ras also could be suppressed.
Amplification of endogenous myc-related DNA sequences in a human myeloid leukaemia cell line
It is demonstrated that sequences in normal human DNA homologous to the avian myc oncogene are present in multiple copies in the chromosomal DNA of the human leukaemia cell line HL-60, and this myc-related gene amplification is not present in other cultured human myeloid leukaems, including K-56214 and KG-115.
Malignant growth in the normal host after variant selection in vitro with cytolytic T-cell lines.
The results strongly suggest that loss of defined components of a complex T-cell-recognized antigen are sufficient to allow escape from immunosurveillance.
Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts
DNAs obtained from human, rabbit and mouse bladder carcinomas lines, a lung carcinoma line and rat neuroblastoma and mouse glioma lines, are able to induce transformation of NIH3T3 cells on transfection.
T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB- and Harvey-MSV transforming genes
A transforming gene isolated from T24 human bladder carcinoma cells is closely related to the BALB murine sarcoma virus (MSV) onc gene (v-bas), which implies that rather subtle genetic alterations have led to the activation of the normal human homologue of v-bas as a human transforming gene.
Three human transforming genes are related to the viral ras oncogenes.
Three distinct transforming genes present in human tumor cell lines are all related to the viral oncogenes of Harvey and Kirsten murine sarcoma viruses, designated v-H-ras and v-K-ras, respectively, and based on the homology with the v-ras genes, they are established to be a third member of the ras gene family, which is called N-ras.