Decreased expression of the amplified mdr1 gene in revertants of multidrug-resistant human myelogenous leukemia K562 occurs without loss of amplified DNA.
Amplification and increased expression of the mdr1 gene associated with multidrug resistance in human tumors were found in multidrug-resistant sublines of human myelogenous leukemia K562 selected with vincristine (K562/VCR) or adriamycin (K562/ADM). In two revertant cell lines of K562/ADM, amplification of the mdr1 gene was maintained at the same level as in K562/ADM, but expression of the 4.5-kilobase mdr1 mRNA was greatly decreased, indicating that amplified genes may be inactivated at the level of transcription without a corresponding loss of amplified DNA.
D004273:DNA, Neoplasm / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics*; D005784:Gene Amplification; D005786:Gene Expression Regulation; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D014750:Vincristine; D004317:Doxorubicin