Mechanisms of 3-hydroxy-3-methylglutaryl coenzyme A reductase overaccumulation in three compactin-resistant cell lines.
We have isolated three mammalian cell lines which are resistant to compactin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The drug resistance in all three cell lines is due to an increase of HMG-CoA reductase activity. Two of the three cell lines overaccumulate HMG-CoA reductase messenger RNA when grown in the presence of compactin. DNA hybridization experiments indicate that both a baby hamster kidney-derived compactin-resistant cell line, C100, and a cell line derived from mouse 3T6 cells, 3T6-40, exhibit amplifications of the HMG-CoA reductase gene. A third compactin-resistant cell line derived from Chinese hamster ovary cells, ML100, does not exhibit an amplification of the HMG-CoA reductase gene, nor does it show an elevated level of HMG-CoA reductase mRNA, comparable to that seen in the other cell lines.
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004247:DNA; D004351:Drug Resistance; D005260:Female; D005784:Gene Amplification; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics* / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007668:Kidney; D008148:Lovastatin / Q000031:analogs & derivatives*; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology*; D009693:Nucleic Acid Hybridization; D010053:Ovary; D012333:RNA, Messenger / Q000378:metabolism*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; D012333:RNA, Messenger; C012258:mevastatin; D004247:DNA; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases