Resistance of tumors to multiple chemotherapeutic agents is often due to the MDR (Multiple Drug Resistance) gene. This gene encodes a protein that acts by which of the following mechanisms?

a. As a transmembrane efflux pump for chemotherapeutic agents

Resistance to chemotherapeutic agents may become manifest during the administration of drugs of very different classes, with a variety of presumed intracellular targets. Such resistance, a function separate from the state of proliferation of the malignant cells, has been termed multidrug resistance. This form of resistance is mediated by the cell surface protein, Pglycoprotein, a product of the MDR-1 gene. A magnesium-dependent ATPase, P-glycoprotein acts as a transmembrane efflux pump and appears to serve as a cellular detoxifier and possibly as a chloride pump. P-glycoprotein causes the extrusion of diverse agents such as anthracyclines, epipodophyllotoxins, Vinca alkaloids, and actinomycins out of the cell before they are able to reach their intracellular targets. The protein is normally found on the luminal surface of such organs as the colon and rectum, small intestine, proximal tubules of the kidney, and gravid uterus; the acinar and bile canalicular surfaces of pancreatic and hepatic parenchymal cells, respectively; and in cells of the adrenal cortex, where there is no polarity to the cell surface location. P-glycoprotein has likewise been found in tumors derived from these organs.

P-glycoprotein can be induced in vitro by exposing cell lines to increasing concentrations of various agents, a phenomenon which also extends to tissues and cell lines not known to normally express significant amounts of P-glycoprotein, such as melanoma, ovarian carcinoma, small cell carcinoma of the lung, and adenocarcinoma of the breast.