FEBS Letters · 1994 · 41 citations · 39 references
MedicineMolecular BiologyPharmacologyCancer PharmacologyGene ExpressionMolecular OncologyCancer TranscriptomicsChemotherapy ResistanceNoncoding Rna In CancerTherapeutic ResistanceDrug Resistance ModulationMultidrug Resistance ModulationReversal Of Drug ResistanceRna Polymerase I ActivityRna Polymerase I FunctionRna Polymerase I RegulationTherapeutic Resistance MechanismsTriple Helix Structure
The human mdr1 gene encodes a transmembrane glycoprotein the over-expression of which is associated with development of multidrug resistance in human tumor cells. A negative modulation of human mdr1 has been attempted via a 27-mer unmodified triple helix-forming oligonucleotide, named 1D, targeted to a homopurine sequence in the coding region of the gene. By administering 10 microM of 1D we could find a significant reduction in MDR1 mRNA levels in the human drug-resistant cell line CEM-VLB100. This effect appears to be specific and due to a transient block of RNA polymerase mediated by triple helix formation.
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