In vitro studies demonstrate that tumor cell lines can become resistant after exposure to various anticancer agents. These cells express a specific cell surface glycoprotein that has which of the following functions?

Question

In vitro studies demonstrate that tumor cell lines can become resistant after exposure to various anticancer agents.  These cells express a specific cell surface glycoprotein that has which of the following functions?

Quizplus · Accepted Answer

Human tumor cells have developed the ability to resist chemotherapy in much the same way that many bacteria have developed resistance to antibiotics. One well-studied mechanism by which human tumor cells resist these agents is via the human multidrug resistance (MDR1) gene. The prototype product of this gene is P-glycoprotein, a transmembrane protein that functions as an ATP-dependent efflux pump. P-glycoprotein is normally expressed in intestinal and renal tubular epithelial cells and functions to eliminate foreign compounds from the body. This protein is also present in the capillary endothelium of the vessels that form the blood-brain barrier. In this location, P-glycoprotein prevents the penetration of foreign compounds into the CNS. In tumor cells, this ATP-powered transmembrane pump protein actively removes chemotherapeutic agents, particularly hydrophobic agents like the anthracyclines. Drugs such as verapamil, diltiazem, and ketoconazole, among others, have been shown to reduce the action of this multidrug resistance protein in experimental models; the development of agents specifically intended to abolish this mechanism of resistance is currently underway. (Choice A) Tyrosine kinase receptors generally mediate the effects of hormones that promote anabolism and cell growth such as insulin, insulin-like growth factor 1, epidermal growth factor, platelet-derived growth factor, and others. (Choice B) cAMP is the second messenger in the G-protein / adenylate cyclase second messenger system. This system is utilized by numerous hormone receptors including beta-adrenergic receptors, V2 ADH receptors, and calcitonin, glucagon, TSH, ACTH, and HCG receptors, among many others. (Choice C) Cell adhesion molecules (CAMs) are proteins located on the cell surface that mediate binding with other cells or with the extracellular matrix. Examples include selectins, integrins, and cadherins. Cell adhesion molecules are generally downregulated in malignant tumors, which allows these cells to spread from their site of origin. (Choice D) Transmembrane ion channels selectively allow certain ions to pass into or out of the cell. These channels facilitate the formation of a voltage gradient across the cell membrane. Examples of ion channels, transporters, and exchangers are ubiquitous. These proteins participate in the formation of urine, nerve and myocyte depolarization, muscle contraction, sweat formation, exocrine secretion formation, and many other processes. Educational Objective: The human multidrug resistance (MDR1) gene codes for P-glycoprotein, a transmembrane ATP-dependent efflux pump protein that has a broad specificity for hydrophobic compounds. This protein can both reduce the influx of drugs into the cytosol and can increase efflux from the cytosol, thereby preventing the action of chemotherapeutic agents.

In Vitro Studies Demonstrate That Tumor Cell Lines Can Become