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 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.
Riordan
J R
JR
Deuchars
K
K
Kartner
N
N
Alon
N
N
Trent
J
J
Ling
V
V
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D005784:Gene Amplification; D005796:Genes; D006023:Glycoproteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D010053:Ovary; D001616:beta-Galactosidase / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006023:Glycoproteins; D004247:DNA; D001616:beta-Galactosidase