Amplification and overexpression of the P‐glycoprotein genes and differential amplification of three other genes in SEWA murine multidrug‐resistant cells

We have previously reported on the derivation of a series of multidrug‐resistant SEWA murine cell lines, independently selected for resistance to actinomycin D, vincristine and colcemid. All exhibited cytogenetic signs of gene amplification, double minutes or homogeneously staining regions. Five different cDNA probes, representing genes amplified in the multidrug resistant Chinese hamster line CH R C5, were hybridized to total DNA from the cell lines. Among the 5 probes, one corresponded to the P‐glycoprotein gene and another to a gene for a 21 kD cytosolic protein (p21). The gene products of the remaining 3 cZNAs were unknown. It was shown that the hamster probes cross‐hybridized to sequences present in the mouse lines. Our results indicate that P‐glycoprotein in the mouse is represented by a family of at least 3 genes. Members of the P‐glycoprotein gene family were shown to be amplified in all the resistant mouse lines. Among the four other genes, three (including the p21 gene) were shown to be amplified in some but not all of the lines. The gene expression of P‐glycoprotein and p21 corresponded to the level of amplification. Our results support recent data showing that P‐glycoprotein gene amplification alone can cause the multidrug resistance phenotype.