Regulation of Multidrug Resistance Phenotype and P-Glycoprotein Activity in MCF-7 Cells by the Epithelial Na+ Channel

摘要

Drug resistance is a process that occurs in a variety of carcinomas and especially in epithelial breast carcinomas. These carcinomas represent (caret)80% of all breast cancer types and are the subject of intense study. The origins of drug resistance in these cells are poorly determined. This proposal deals with examining the roles of the cell membrane and the properties of ion channels within this membrane in drug resistance. It is well known that the plasma membrane, through its role as a permeability barrier that defines and differentiates the intracellular from the extracellular one, plays a vital role in cell viability and survival to various noxious agents. However, the transport properties of breast epithelial cells and certainly those of cancerous origins are essentially undetermined. We propose to define these properties and to test the effects of transport alterations on cell viability and resistance to anthracycline antibiotics, agents which are widely used to combat breast cancer. Moreover, the routes of drug entry and exist across polarized cells (with apical and basolateral membranes) will be determined.