Differential amplification and disproportionate expression of five genes in three multidrug-resistant Chinese hamster lung cell lines.
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.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D002460:Cell Line; D003078:Colchicine / Q000633:toxicity; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000235:genetics; D004351:Drug Resistance; D005260:Female; D005784:Gene Amplification; D005796:Genes / Q000187:drug effects; D008040:Genetic Linkage; D006023:Glycoproteins / Q000235:genetics; D010053:Ovary; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D014158:Transcription, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006023:Glycoproteins; D012333:RNA, Messenger; D004247:DNA; D003078:Colchicine