Increased epidermal growth factor receptor in multidrug‐resistant human neuroblastoma cells

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Abstract
Multidrug‐resistant human neuroblastoma cell lines obtained by selection with vincristine or actinomycin D from two independent clonal lines, SH‐SY5Y and MCIXC, have 3‐ to 30‐fold more cell surface epidermal growth factor (EGF) receptors than the drug‐sensitive parental cells as indicated by EGF binding assays and immunoprecipitation, affinity‐labeling, and phosphorylation studies. Reversion to drug sensitivity in one line was accompanied by a return to the parental level of EGF receptor. SH‐EP cells, a clone derived from the same neuroblastoma cell line as SH‐SY5Y but which displays melanocyte rather than neuronal lineage markers, also express significantly more EGF receptor than SH‐SY5Y cells. By nucleic acid hybridization analysis with a molecularly cloned probe, increased receptor level in multidrug‐resistant cells was shown to be the result of higher levels of EGF receptor mRNA in drug‐resistant than in drug‐sensitive cells. The increased steady state amount of specific RNA did not result from amplification of receptor‐encoding genes. A small difference was observed in the electrophoretic mobility under denaturing conditions of EGF receptor immunoprecipitated from drug‐resistant and drug‐sensitive cells. Quantitative and qualitative modulation of the EGF receptor might reflect alterations in the transformation and/or differentiation phenotype of the resistant cells or might result from unknown selective pressures associated with the development of multidrug resistance.