Identification of a novel calcium-binding protein (CP22) in multidrug-resistant murine and hamster cells

Analysis of cytoplasmic extracts of multidrug-resistant murine and hamster cells by SDS gel and 2D gel electrophoresis showed that they expressed an abundant 22 kDa protein which was absent from the drug-sensitive parent lines. SDS gel electrophoresis in the presence of EGTA and direct binding tests with 45Ca2+ showed that the resistance-associated protein is a specific calcium-binding protein. Thus the development of multidrug resistance in both colchicine-selected hamster cells and adriamycin-selected murine cells is associated with a major change in calcium metabolism. These observations provide the first molecular basis for the hypothesis that Ca2+ plays a central role in the development of the multidrug resistance phenomenon.