Expression of activated rat neu oncogene is sufficient to induce experimental metastasis in 3T3 cells

Amplification or overexpression of the human neu oncogene has been shown to correlate with the number of lymph node metastases in breast cancer patients, suggesting that expression of the neu oncogene may be associated with increased metastatic potential. However, there has been no systematic study on the role of the neu oncogene in metastasis to support this correlation. In our study, mouse embryo fibroblast 3T3 cells transformed by the mutation-activated rat neu oncogene exhibited metastatic properties both in vitro and in vivo, while parental 3T3 cells did not. Monoclonal antibodies capable of inducing down-regulation of the neu-encoded p185 protein reduced the metastatic potential induced by neu. These data provide strong experimental evidence that neu oncogene expression is sufficient for the induction of metastasis in the 3T3 cell system and supply a molecular basis supporting the correlations found in clinical observation. The results also suggest that neu-specific monoclonal antibodies may have preventative or therapeutic potential for neu-induced metastasis.