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

Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines 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 (Mr) 170,000 (P-glycoprotein) is consistently found in different multidrug-resistant human and animal cell lines, and in transplantable tumours1,2,6–10. 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Springer Journals

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

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References (21)

Publisher
Springer Journals
Copyright
Copyright © 1985 by Nature Publishing Group
Subject
Science, Humanities and Social Sciences, multidisciplinary; Science, Humanities and Social Sciences, multidisciplinary; Science, multidisciplinary
ISSN
0028-0836
eISSN
1476-4687
DOI
10.1038/316817a0
Publisher site
See Article on Publisher Site

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 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 (Mr) 170,000 (P-glycoprotein) is consistently found in different multidrug-resistant human and animal cell lines, and in transplantable tumours1,2,6–10. 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.

Journal

Nature – Springer Journals

Published: Aug 29, 1985

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