Altered Expression of Epidermal Growth Factor Receptor Gene in a Classical Multidrug‐resistant Variant of a Human Cancer Cell Line, KB

Abstract

A variant clone resistant to high doses of colchicine (KB‐C1) derived from human cancer KB cell line is resistant to various anticancer agents. The KB‐C1 cells were much more resistant to epidermal growth factor and a chimeric toxin, EGF‐Pseudomottas exotoxin (PE), than the parental KB cells. KB‐C1 cells have decreased numbers of EGF‐receptors, though the affinity of the receptors is similar to that in the parental KB cells. A drug‐sensitive revertant (C1‐R2) partially recovered its EGF‐receptor activity. Northern blot analysis showed a decreased level of EGF‐receptor mRNA in KB‐C1 cells, while the multidrug‐resistance gene, mdr‐1, was expressed at very high levels in KB‐C1 cells, but not in KB or C1‐R2 cells. The drug‐resistant cells were less tumorigenic than the parental cells when injected into nude mice. A decreased expression of EGF‐receptor in these cells may be one of the pleiotropic properties of multidrug‐resistant cells and may perhaps represent the basis for their reduced tumorigenicity.