Human KB cells which are resistant to adriamycin (A), vinblastine (V), colchicine (C) and actinomycin (D) (AcD) have been shown to contain an amplified gene (mdr-l) responsible for the drug resistance. A fragment of this gene has been cloned and used to screen a cDNA library and identify cDNAs encoding a 170 kdalton membrane protein also found to be increased in multidrug resistant cells. The 170 kd protein binds vinblastine and related drugs, and this binding is overcome by drugs such as verapamil, quinidine, and diltiazem which overcome multidrug resistance. The levels of expression of the mdr-l gene are being measured in human cancers.
