Mitogenic activity of the epidermal growth factor receptor after transfer from A431 carcinoma cells to receptor-negative fibroblastic cells.

This paper demonstrates spontaneous transfer of epidermal growth factor (EGF) receptor mitogenicity from human A431 carcinoma cells to receptor negative mouse cells. The fact of transfer was documented by the demonstration in the recipient cell of normal EGF-binding affinity, covalent labeling of transferred receptor by 125I-EGF, and reactivity with specific anti-human receptor antibody. Phosphorylation experiments suggest that in the transferred receptor the protein kinase site tends to face the inside of the cell. The transferred receptor imposed upon the normally unresponsive cells a mitogenic responsiveness to EGF in the nM concentration range, as measured by stimulation of DNA replication. EGF-dependent mitogenesis in the recipient cells was abolished by both anti-EGF antibody and anti-human receptor antibody, indicating that the transferred mitogenicity is both EGF and receptor specific. For NR-6 cells without transplanted receptor, the same antibody had no effect on non-EGF-dependent mitogenesis. Interestingly, although the transferred receptor displayed normal behavior in several respects, it did not mediate rapid internalization and degradation of bound EGF.