Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines

Nature. 1985 Aug 29-Sep 4;316(6031):817-9. doi: 10.1038/316817a0.

Abstract

The multidrug-resistance phenotype expressed in mammalian cell lines is complex. Cells selected with a single agent can acquire cross-resistance to a remarkably wide range of compounds which have no obvious structural or functional similarities. The basis for cross-resistance seems to be a decreased net cellular accumulation of the drug involved, and has been attributed to alterations in the plasma membrane. An over-expressed plasma membrane glycoprotein of relative molecular mass (Mr) 170,000 (P-glycoprotein) is consistently found in different multidrug-resistant human and animal cell lines, and in transplantable tumours. Consequently, it has been postulated that P-glycoprotein directly or indirectly mediates multidrug resistance. Here we report the cloning of a complementary DNA encoding P-glycoprotein. Southern blot analysis of hamster, mouse and human DNA using this cDNA as a probe showed that P-glycoprotein is conserved and is probably encoded by a gene family, and that members of this putative family are amplified in multidrug-resistant cells.

Publication types

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

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Animals
  • Base Sequence
  • Cell Line
  • Cloning, Molecular
  • Cricetinae
  • Cricetulus
  • DNA / metabolism
  • Drug Resistance
  • Female
  • Gene Amplification*
  • Genes*
  • Glycoproteins / genetics*
  • Nucleic Acid Hybridization
  • Ovary
  • beta-Galactosidase / genetics

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Glycoproteins
  • DNA
  • beta-Galactosidase