O-11: High-Content Screening Methods for Activity Assays of Multidrug Resistance Proteins in Cancer Cell Lines (Pages: 22-23)

Pulaski L *, Studzian M , Mazurek A , Bartosz G ,


Multidrug resistance, mediated by active export pumps extruding anticancer drug molecules out of cells, is a major clinical problem in modern oncology and leads directly to therapy failure and death in hundreds of thousands of patients annually worldwide. The proteins responsible for this phenomenon at the molecular level blong to the ABC protein superfamily and are characterised by a versatile mechanism of action based on poly-specific substrate binding sites and rigid membrane topology with transport power stroke mediated by ATP binding rather than hydrolysis. It is known that subtle changes in the amino acid sequence Abstract of the 1st Int. Student Congress on Cell & Molecular Medicine Cell Journal(Yakhteh), Vol 12, Suppl 1, Winter 2011 23 (including some naturally occurring genetic variants) can cause distinct variations in activity and substrate specificity of these proteins, therefore we embarked on a study of some molecular determinants of activity by molecular engineering