Nature 316, 817 - 819 (29 August 1985); doi:10.1038/316817a0

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

John R. Riordan^*, Kathryn Deuchars^†, Norbert Kartner^†, Noa Alon^*, Jeffrey Trent^† & Victor Ling^†

^*Research Institute, Hospital for Sick Children, and Departments of Biochemistry and Clinical Biochemistry, University of Toronto, Toronto, Ontario, Canada M5G 1X8
^†Ontario Cancer Institute, Princess Margaret Hospital and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M4X 1K9
^‡Department of Internal Medicine and the Cancer Center, University of Arizona, Tucson, Arizona 85724, USA

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 similarities¹⁻⁶. The basis for cross-resistance seems to be a decreased net cellular accumulation of the drugs involved, and has been attributed to alterations in the plasma membrane. An over-expressed plasma membrane glycoprotein of relative molecular mass (M_r) 170,000 (P-glycoprotein) is consistently found in different multidrug-resistant human and animal cell lines, and in transplantable tumours^1,2,6−10. Consequently, it has been postulated that P-glycoprotein directly or indirectly mediates multidrug resistance⁷⁻¹¹. 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.

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