Antiproliferative effects of antisense oligonucleotides directed to the RNA of c-myc oncogene.
Several groups have reported the use of antisense oligonucleotides to inhibit c-myc gene expression and study its biological role. However high concentrations of free oligonucleotides were generally needed. To lower their concentration and stabilize the antisense effect against c-myc, oligonucleotides were covalently linked to poly(L-lysine) and administered in ternary complexes formed with heparin (100 micrograms/ml). A sequence specific growth inhibition was observed at concentrations lower than 1 microM, while oligonucleotide-poly(L-lysine) conjugates alone were inefficient. Similar results occurred with other polyanionic compounds. Inhibition of proliferation was correlated to a reduction of c-myc protein and to a transient decrease in c-myc mRNA level. However, implication of RNase H in this process could not be demonstrated.
Degols
G
G
Laboratoire de Biochimie des Proteines, UA CNRS 1191, Université de Montpellier II, France.
Leonetti
J P
JP
Mechti
N
N
Lebleu
B
B
D001483:Base Sequence; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000235:genetics*; D012313:RNA / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D012259:Ribonuclease, Pancreatic
D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012313:RNA; D012259:Ribonuclease, Pancreatic