Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line.
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.
Cole
S P
SP
Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada.
Bhardwaj
G
G
Gerlach
J H
JH
Mackie
J E
JE
Grant
C E
CE
Almquist
K C
KC
Stewart
A J
AJ
Kurz
E U
EU
Duncan
A M
AM
Deeley
R G
RG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000595:Amino Acid Sequence; D000818:Animals; D002871:Chromosome Banding; D002885:Chromosomes, Human, Pair 16; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics*; D005784:Gene Amplification; D006801:Humans; D008168:Lung / Q000502:physiology; D008175:Lung Neoplasms; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000502:physiology; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D004317:Doxorubicin