title: The human multidrug resistance (mdr1) gene. cDNA cloning and transcription initiation.
abstract: Multidrug resistance in human KB carcinoma cells selected for resistance to colchicine, vinblastine, or adriamycin results from overexpression, and frequently amplification, of a specific gene (mdr1). Overlapping cDNA clones representing a complete 4.7-kilobase mdr1 transcript have been obtained from multidrug-resistant KB cells. Primer extension and S1 nuclease protection experiments show that two transcripts initiate 136 and 140 bases upstream from the first ATG codon in all human multidrug-resistant cell lines. The mdr1 gene is expressed in human normal kidney cells and HepG2 liver cells as a poly(A)+ RNA which starts from the same sites. Less prominent transcripts were found to initiate 155-180 bases upstream from the first ATG codon in vinblastine- or adriamycin-selected cell lines and 480-630 bases upstream in colchicine-selected cell lines. Southern hybridization analyses with different portions of a full-length cDNA indicate that the human mdr1 gene encompasses at least 70 kilobases of DNA amplified in all highly multidrug-resistant cell lines.
mesh_terms: D001483:Base Sequence; D003001:Cloning, Molecular; D003078:Colchicine / Q000633:toxicity; D004247:DNA / Q000378:metabolism*; D004262:DNA Restriction Enzymes; D004317:Doxorubicin / Q000633:toxicity; D004351:Drug Resistance; D005784:Gene Amplification; D005796:Genes; D006801:Humans; D007624:KB Cells; D009693:Nucleic Acid Hybridization; D014158:Transcription, Genetic; D014747:Vinblastine / Q000633:toxicity
chemical_list: D014747:Vinblastine; D004317:Doxorubicin; D004247:DNA; D004262:DNA Restriction Enzymes; D003078:Colchicine