title: Coamplification of 3-hydroxy-3-methylglutaryl coenzyme A reductase genes in methotrexate-resistant human leukemia cell lines.
abstract: Methotrexate (MTX)-resistant K562 human myelocytic leukemia sublines with 20- and 200-fold amplified dihydrofolate reductase (DHFR) genes localized to homogeneously staining regions (HSRs) on the long arms of chromosomes 5, 6, and 19 were used to examine whether other genes mapping close to the DHFR genes were coamplified. The gene for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, located on chromosome 5q13.3-14, was coamplified 4-14-fold, corresponding to the levels of resistance exhibited by these cells. Similar observations were made with a MTX-resistant subline of the promyelocytic leukemia cell line, HL-60R, with 200 gene copies of DHFR. These observations indicate a tight linkage of DHFR and HMG-CoA genes on chromosome 5q.
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: S
authors.initials: S
authors.lastname: Srimatkandada
authors.forename: S K
authors.initials: SK
authors.lastname: Dube
authors.forename: M
authors.initials: M
authors.lastname: Carmen
authors.forename: J R
authors.initials: JR
authors.lastname: Bertino
mesh_terms: D015152:Blotting, Northern; D015139:Blotting, Southern; D004247:DNA / Q000032:analysis*; D004351:Drug Resistance; D005784:Gene Amplification / Q000235:genetics*; D018922:HL-60 Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics* / Q000378:metabolism; D020014:K562 Cells / Q000187:drug effects / Q000201:enzymology; D007938:Leukemia / Q000201:enzymology / Q000235:genetics*; D008727:Methotrexate / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000201:enzymology
chemical_list: D012333:RNA, Messenger; D004247:DNA; D006903:Hydroxymethylglutaryl CoA Reductases; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate