Cell
Volume 41, Issue 3, July 1985, Pages 695-706
Journal home page for Cell

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

https://doi.org/10.1016/S0092-8674(85)80050-7Get rights and content

Summary

Exposure of neu-oncogene-transformed NIH 3T3 cells to monoclonal antibodies reactive with the neu gene product, p185, results in the rapid and reversible loss of both cell-surface and total cellular p185. Although not directly cytotoxic, monoclonal anti-p185 antibody treatment causes neu-transformed NIH 3T3 cells to revert to a nontransformed phenotype, as determined by anchorage-independent growth. Isotype matched control antibodies of an unrelated specificity do not affect p185 levels or colony formation in soft agar by neu-transformed NIH 3T3 cells. Soft agar colony formation by NIH 3T3 cells transformed by ras oncogenes is not affected by anti-p185 antibody treatment. Anchorage-independent growth of cells from the ethyl nitrosourea-induced rat neuroblastoma line in which neu was originally detected by DNA transfection is also inhibited in the presence of anti-p185 monoclonal antibodies. Collectively, these results suggest that p185 is required to maintain transformation induced by the neu oncogene.

References (55)

  • BadgerC.C. et al.

    Therapy of murine leukemia with monoclonal antibody against a normal differentiation antigen

    J. Exp. Med.

    (1984)
  • BishopJ.M.

    Cellular oncogenes and retroviruses

    Ann. Rev. Biochem.

    (1983)
  • BishopJ.M. et al.

    Function and origins of retroviral transforming genes

  • BoyseE.A. et al.

    Modification of the antigenic structure of the cell membrane by thymus-leukemia (TL) antibody

  • CarpenterG. et al.

    Epidermal growth factor

    Ann. Rev. Biochem.

    (1979)
  • CollinsS. et al.

    Amplification of endogenous mycrelated DNA sequences in a human myeloid leukemia cell line

    Nature

    (1982)
  • CooperC.S. et al.

    Molecular cloning of a new transforming gene from a chemically transformed human cell line

    Nature

    (1984)
  • CooperG.M.

    Cellular transforming genes

    Science

    (1982)
  • CzechM.P. et al.

    Interrelationships among receptor structures for insulin and peptide growth factors

  • de KleinA. et al.

    A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelogenous leukemia

    Nature

    (1982)
  • DerC.J. et al.

    Transforming genes of human bladder and lung carcinoma lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses

  • DownwardJ. et al.

    Close similarity of epidermal growth factor receptor and v-erbB oncogene protein sequences

    Nature

    (1984)
  • DrebinJ.A. et al.

    Monoclonal antibodies identify a cell surface antigen associated with an activated cellular oncogene

    Nature

    (1984)
  • EdelmanG.M.

    Surface modulation in cell recognition and cell growth

    Science

    (1976)
  • EvaA. et al.

    Cellular genes analogous to retroviral onc genes are transcribed in human tumor cells

    Nature

    (1982)
  • FreedmanV. et al.

    Cellular tumorigenicity in nude mice: correlation with cell growth in semi-solid medium

    Cell

    (1974)
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