Increased epidermal growth factor receptor in multidrug-resistant human neuroblastoma cells.
Multidrug-resistant human neuroblastoma cell lines obtained by selection with vincristine or actinomycin D from two independent clonal lines, SH-SY5Y and MC-IXC, 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.
Meyers
M B
MB
Laboratory of Cellular and Biochemical Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Shen
W P
WP
Spengler
B A
BA
Ciccarone
V
V
O'Brien
J P
JP
Donner
D B
DB
Furth
M E
ME
Biedler
J L
JL
D015152:Blotting, Northern; D015139:Blotting, Southern; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004351:Drug Resistance; D004586:Electrophoresis; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism*; D010766:Phosphorylation; D012313:RNA / Q000032:analysis; D014750:Vincristine / Q000494:pharmacology
D003609:Dactinomycin; D014750:Vincristine; D012313:RNA; D066246:ErbB Receptors