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Updated: Aug 11, 2026
A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells
Published on: July 3, 2013
Differential amplification and disproportionate expression of five genes in three multidrug-resistant Chinese hamster
Abstract:
At least five linked genes are amplified in the multidrug-resistant Chinese hamster ovary cell line CHRC5, selected with colchicine (A. M. Van der Bliek, T. Van der Velde-Koerts, V. Ling, and P. Borst, Mol. Cell. Biol. 6:1671-1678, 1986). We report here that only a subset of these, encoding the 170-kilodalton P-glycoprotein, are consistently amplified in three different multidrug-resistant Chinese hamster lung cell lines, selected with vincristine, daunorubicin, or actinomycin D. Within each cell line, genomic sequences homologous to the P-glycoprotein cDNA probe were amplified to different levels. The pattern of differential amplification was consistent with the presence of at least two and possibly three P-glycoprotein genes. In the actinomycin D-selected cell line, these genes were disproportionately overexpressed relative to the associated levels of amplification. These results underline a central role for P-glycoprotein in multidrug resistance. In the daunorubicin-selected cell line, another, as yet uncharacterized, gene was amplified but disproportionately underexpressed. Its amplification was therefore fortuitous. We present a tentative map of the region in the hamster genome that is amplified in the multidrug-resistant cell lines which were analyzed.
Insights
P-glycoprotein gene amplification is central to multidrug resistance in hamster cells. Differential gene amplification and overexpression highlight its role, with some amplified genes showing fortuitous underexpression.
Area of Science:
- Molecular biology
- Genetics
- Cell biology
Background:
- Multidrug resistance (MDR) in cancer cells is a significant clinical challenge.
- Gene amplification is a known mechanism contributing to MDR.
- Previous studies identified gene amplification in multidrug-resistant Chinese hamster ovary cells.
Purpose of the Study:
- To investigate the amplification patterns of P-glycoprotein genes in different multidrug-resistant Chinese hamster lung cell lines.
- To determine the relationship between gene amplification levels and P-glycoprotein expression.
- To identify other potentially amplified genes in drug-resistant cells.
Main Methods:
- Selection of Chinese hamster lung cell lines with various drugs (vincristine, daunorubicin, actinomycin D).
- Analysis of gene amplification using P-glycoprotein cDNA probes.
- Quantitative assessment of gene amplification levels and gene expression.
- Genomic mapping of amplified regions.
Main Results:
- Consistent amplification of P-glycoprotein encoding genes across three distinct multidrug-resistant cell lines.
- Differential amplification levels of P-glycoprotein genes, suggesting multiple gene copies.
- Disproportionate overexpression of P-glycoprotein genes in actinomycin D-selected cells.
- Amplification and underexpression of an uncharacterized gene in daunorubicin-selected cells.
Conclusions:
- P-glycoprotein plays a central role in multidrug resistance.
- Differential gene amplification and expression are key features of drug resistance.
- The study provides a tentative map of amplified genomic regions in drug-resistant hamster cells.
