학술논문

Overexpression of a Transporter Gene in a Multidrug-Resistant Human Lung Cancer Cell Line
Document Type
research-article
Source
Science, 1992 Dec 01. 258(5088), 1650-1654.
Subject
Cell lines
Messenger RNA
HeLa cells
Complementary DNA
RNA
Amino acids
DNA
ATP binding cassette transporters
Lung neoplasms
Chromosomes
Language
English
ISSN
00368075
10959203
Abstract
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.