Effect of unmodified triple helix-forming oligodeoxyribonucleotide targeted to human multidrug-resistance gene mdr1 in MDR cancer cells.
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.
Scaggiante
B
B
Department of Biomedical Sciences and Technologies, University of Udine, Italy.
Morassutti
C
C
Tolazzi
G
G
Michelutti
A
A
Baccarani
M
M
Quadrifoglio
F
F
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D018432:Drug Resistance, Multiple / Q000235:genetics*; D006801:Humans; D007938:Leukemia; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000187:drug effects; D013873:Thionucleotides; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D013873:Thionucleotides