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

J Cell Biochem. 1988 Oct;38(2):87-97. doi: 10.1002/jcb.240380203.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Northern
  • Blotting, Southern
  • Cells, Cultured
  • Dactinomycin / pharmacology
  • Drug Resistance
  • Electrophoresis
  • ErbB Receptors / analysis*
  • ErbB Receptors / genetics
  • Humans
  • Neuroblastoma / metabolism*
  • Phosphorylation
  • RNA / analysis
  • Vincristine / pharmacology

Substances

  • Dactinomycin
  • Vincristine
  • RNA
  • ErbB Receptors