Expression of hamster P-glycoprotein and multidrug resistance in DNA-mediated transformants of mouse LTA cells.
The overexpression of a plasma membrane glycoprotein, P-glycoprotein, is strongly correlated with the expression of multidrug resistance. This phenotype (frequently observed in cell lines selected for resistance to a single drug) is characterized by cross resistance to many drugs, some of which are used in cancer chemotherapy. In the present study we showed that DNA-mediated transformants of mouse LTA cells with DNA from multidrug-resistant hamster cells acquired the multidrug resistance phenotype, that the transformants contained hamster P-glycoprotein DNA sequences, that these sequences were amplified whereas the recipient mouse P-glycoprotein sequences remained at wild-type levels, and that the overexpressed P-glycoprotein in these cells was of hamster origin. Furthermore, we showed that the hamster P-glycoprotein sequences were transfected independently of a group of genes that were originally coamplified and linked within a 1-megabase-pair region in the donor hamster genome. These data indicate that the high expression of P-glycoprotein is the only alteration required to mediate multidrug resistance.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D006224:Cricetinae; D004351:Drug Resistance; D005784:Gene Amplification; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D007163:Immunosorbent Techniques; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D014170:Transformation, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D006023:Glycoproteins; D008565:Membrane Proteins