Gene amplification and drug resistance in cultured animal cells

Gene amplification-multiplication is an often observed phenomenon in biological systems. In 1925 Sturtevant first reported a ‘quantitative’ genetic change at the ‘bobbed’ locus in Drosophila melanogaster: a change in ribosomal gene copy number (45). Gene duplications are common in bacterial systems (3). Developmental regulation of gene amplification was first shown for ribosomal genes in Xenopus laevis ooctyes (12), and more recently with chorion genes in the ovary during oogenesis in Drosophila melanogaster (44). During the past six years the study of gene amplification has received new impetus with the findings that a number of specific genes can undergo selective amplification when somatic mammalian cells are placed under selective conditions (41). The frequencies with which such cells can undergo gene amplification is greater than standard mutation rates, suggesting that when ceils are placed in selective conditions where survival is based on overproduction of a protein, gene amplification is a likely mechanism for survival and growth of such cells. This paper reviews the current status of gene amplifications, in particular in cultured somatic cells of mammalian origin.