DNA-mediated transfer of multiple drug resistance and plasma membrane glycoprotein expression

1982 ◽  
Vol 2 (8) ◽  
pp. 881-889
Author(s):  
P G Debenham ◽  
N Kartner ◽  
L Siminovitch ◽  
J R Riordan ◽  
V Ling
Keyword(s):  
Drug Resistance ◽  
Plasma Membranes ◽  
Multiple Drug Resistance ◽  
Chinese Hamster ◽  
Surface Glycoprotein ◽  
Multiple Drug ◽  
Cell Surface Glycoprotein ◽  
Resistance Phenotype ◽  
P Glycoprotein ◽  
Wide Range

Colchicine-resistant Chinese hamster ovary (CHO) cell mutants whose resistance results from reduced drug permeability have been isolated previously in our laboratories. This reduced permeability affects a wide range of unrelated drugs, resulting in the mutants displaying a multiple drug resistance phenotype. A 170,000-dalton cell surface glycoprotein (P-glycoprotein) was identified, and its expression appears to correlate with the degree of resistance. In this study we were able to confer the multiple drug resistance phenotype on sensitive mouse L cells by DNA-mediated gene transfer of DNA obtained from the colchicine-resistant mutants. P-glycoprotein was detected in plasma membranes of these DNA transformants by staining with an antiserum raised against membranes of mutant CHO cells. These results are consistent with a causal relationship between P-glycoprotein expression and the multiple drug resistance phenotype.

scholarly journals DNA-mediated transfer of multiple drug resistance and plasma membrane glycoprotein expression.

1982 ◽  
Vol 2 (8) ◽  
pp. 881-889 ◽  
Author(s):  
P G Debenham ◽  
N Kartner ◽  
L Siminovitch ◽  
J R Riordan ◽  
V Ling
Keyword(s):  
Drug Resistance ◽  
Plasma Membranes ◽  
Multiple Drug Resistance ◽  
Chinese Hamster ◽  
Surface Glycoprotein ◽  
Multiple Drug ◽  
Cell Surface Glycoprotein ◽  
Resistance Phenotype ◽  
P Glycoprotein ◽  
Wide Range

Colchicine-resistant Chinese hamster ovary (CHO) cell mutants whose resistance results from reduced drug permeability have been isolated previously in our laboratories. This reduced permeability affects a wide range of unrelated drugs, resulting in the mutants displaying a multiple drug resistance phenotype. A 170,000-dalton cell surface glycoprotein (P-glycoprotein) was identified, and its expression appears to correlate with the degree of resistance. In this study we were able to confer the multiple drug resistance phenotype on sensitive mouse L cells by DNA-mediated gene transfer of DNA obtained from the colchicine-resistant mutants. P-glycoprotein was detected in plasma membranes of these DNA transformants by staining with an antiserum raised against membranes of mutant CHO cells. These results are consistent with a causal relationship between P-glycoprotein expression and the multiple drug resistance phenotype.

scholarly journals Chemosensitizing multiple drug resistance of human carcinoma by bicyclol involves attenuated P-glycoprotein, GST-P and Bcl-2

2006 ◽  
Vol 5 (5) ◽  
pp. 536-543 ◽  
Author(s):  
Bing Zhu ◽  
Geng Tao Liu ◽  
Yong Mei Zhao ◽  
Ruo Su Wu ◽  
Samuel J Strada
Keyword(s):  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Human Carcinoma ◽  
P Glycoprotein

Reversion of the multiple-drug resistance phenotype mediated by short interfering RNAs

2005 ◽  
Vol 54 (5) ◽  
pp. 1298-1305 ◽  
Author(s):  
E. B. Logashenko ◽  
A. V. Vladimirova ◽  
A. N. Zenkov ◽  
M. N. Repkova ◽  
A. G. Ven'yaminova ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Resistance Phenotype

Specifically activated dendritic cells—Cell-based vaccine against lymphosarcoma exhibiting multiple drug resistance phenotype

2009 ◽  
Vol 428 (1) ◽  
pp. 252-256
Author(s):  
N. L. Mironova ◽  
E. E. Panzinskyi ◽  
N. A. Popova ◽  
V. P. Nikolin ◽  
M. A. Zenkova ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dendritic Cells ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Resistance Phenotype

scholarly journals In Situ Biochemical Demonstration That P-Glycoprotein Is a Drug Efflux Pump with Broad Specificity

2000 ◽  
Vol 148 (5) ◽  
pp. 863-870 ◽  
Author(s):  
Yu Chen ◽  
Sanford M. Simon
Keyword(s):  
Fluorescent Protein ◽  
Efflux Pump ◽  
Multiple Drug Resistance ◽  
Living Cells ◽  
Drug Accumulation ◽  
Multiple Drug ◽  
Gfp Expression ◽  
Active Efflux ◽  
P Glycoprotein ◽  
Wide Range

While P-glycoprotein (Pgp) is the most studied protein involved in resistance to anti-cancer drugs, its mechanism of action is still under debate. Studies of Pgp have used cell lines selected with chemotherapeutics which may have developed many mechanisms of resistance. To eliminate the confounding effects of drug selection on understanding the action of Pgp, we studied cells transiently transfected with a Pgp-green fluorescent protein (GFP) fusion protein. This method generated a mixed population of unselected cells with a wide range of Pgp-GFP expression levels and allowed simultaneous measurements of Pgp level and drug accumulation in living cells. The results showed that Pgp-GFP expression was inversely related to the accumulation of chemotherapeutic drugs. The reduction in drug concentration was reversed by agents that block multiple drug resistance (MDR) and by the UIC2 anti-Pgp antibody. Quantitative analysis revealed an inverse linear relationship between the fluorescence of Pgp-GFP and MDR dyes. This suggests that Pgp levels alone limit drug accumulation by active efflux; cooperativity between enzyme, substrate, or inhibitor molecules is not required. Additionally, Pgp-GFP expression did not change cellular pH. Our study demonstrates the value of using GFP fusion proteins for quantitative biochemistry in living cells.

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