Pleiotropic drug resistance, protein overexpression, and cytogenetic signs of gene amplification in mouse tumor cells.

We have isolated pleiotropic drug resistant mouse tumor cell lines with resistance-associated double minute chromosomes (DM) or homogeneously staining regions (HSR). In resistant cells, two-dimensional protein electrophoresis revealed elevated levels of a 21,000 dalton protein. Two resistant lines, with cytogenetically unstable (DM) and stable (HSR) gene amplification, were grown in the absence of drug for several weeks. The resistance and the protein overexpression was correlated to the presence of either HSR or DM. This suggests that the 21,000 dalton protein is a gene amplification product, and its importance for the resistance is discussed.