Autocrine inhibition of the epidermal growth factor receptor by intracellular expression of a single-chain antibody.
A gene encoding a single-chain antibody which specifically binds the human epidermal growth factor (EGF) receptor has been constructed and expressed intracellularly. The single-chain antibody is derived from monoclonal antibody 225 which competes with EGF for binding to the extracellular domain of the receptor. The single-chain antibody was provided with a signal peptide to direct it to the secretory pathway and was expressed in EGF receptor transformed NIH/3T3 fibroblasts. EGF induced activation of its receptor was reduced in these cells. In addition, EGF-induced anchorage-independent growth of the cells was inhibited. The data suggest that the single-chain antibody functions in an autocrine fashion to inhibit the activity of the EGF receptor.
Friedrich Miescher-Institut, Basel, Switzerland.
R R
RR
Beerli
W
W
Wels
N E
NE
Hynes
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000276:immunology; D002461:Cell Line, Transformed; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data
D007128:Immunoglobulin Fragments; C055966:immunoglobulin Fv; D066246:ErbB Receptors