OVEREXPRESSION OF A TRANSPORTER GENE IN A MULTIDRUG-RESISTANT HUMAN LUNG-CANCER CELL-LINE

被引:2961
作者
COLE, SPC [1 ]
BHARDWAJ, G [1 ]
GERLACH, JH [1 ]
MACKIE, JE [1 ]
GRANT, CE [1 ]
ALMQUIST, KC [1 ]
STEWART, AJ [1 ]
KURZ, EU [1 ]
DUNCAN, AMV [1 ]
DEELEY, RG [1 ]
机构
[1] KINGSTON GEN HOSP,DEPT PATHOL,KINGSTON K7L 2V7,ONTARIO,CANADA
关键词
D O I
10.1126/science.1360704
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The doxorubicin-selected lung cancer cell line H69AR is resistant to many chemotherapeutic agents. However, like most tumor samples from individuals with this disease, it does not overexpress P-glycoprotein, a transmembrane transport protein that is dependent on adenosine triphosphate (ATP) and is associated with multidrug resistance. Complementary DNA (cDNA) clones corresponding to messenger RNAs (mRNAs) overexpressed in H69AR cells were isolated. One cDNA hybridized to an mRNA of 7.8 to 8.2 kilobases that was 100- to 200-fold more expressed in H69AR cells relative to drug-sensitive parental H69 cells. Overexpression was associated with amplification of the cognate gene located on chromosome 16 at band p13.1. Reversion to drug sensitivity was associated with loss of gene amplification and a marked decrease in mRNA expression. The mRNA encodes a member of the ATP-binding cassette transmembrane transporter superfamily.
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页码:1650 / 1654
页数:5
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