Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies.
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 ethylnitrosourea-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.
Drebin
J A
JA
Link
V C
VC
Stern
D F
DF
Weinberg
R A
RA
Greene
M I
MI
D000818:Animals; D000911:Antibodies, Monoclonal; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002999:Clone Cells; D006251:Harvey murine sarcoma virus / Q000502:physiology; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology; D009857:Oncogenes; D010641:Phenotype; D010750:Phosphoproteins / Q000276:immunology / Q000502:physiology*; D018719:Erb-b2 Receptor Tyrosine Kinases; D014162:Transfection
D000911:Antibodies, Monoclonal; D010750:Phosphoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases