title: Inhibition of cell adhesion to plastic substratum by phosphorothioate oligonucleotide.
abstract: Antisense oligonucleotides have been widely used to achieve specific inhibition of targeted gene expression. However, the mechanism of action is not well understood and in many systems sequence-independent effects occur. We have recently shown that chronic administration of an antisense c-myc phosphorothioate oligonucleotide can specifically inhibit expression of the c-myc protein and growth in human breast cancer cells. We now identify an additional effect of the same oligonucleotide on cell adhesion. Transient delivery through electroporation of 2.5 microM antisense-myc oligonucleotide to MCF-7 cells results in 85% inhibition of adhesion to plastic substratum within 24 h. Both the onset of this effect and the subsequent recovery occur without a change in cell viability, growth, or alteration of adhesion to Matrigel, collagen IV, laminin, or fibronectin. However, no parallel changes in c-myc mRNA or protein expression are detectable, suggesting that in this instance inhibition of adhesion caused by antisense-myc oligonucleotide may involve a mechanism independent of the target sequence.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: P H
authors.initials: PH
authors.lastname: Watson
authors.forename: R T
authors.initials: RT
authors.lastname: Pon
authors.forename: R P
authors.initials: RP
authors.lastname: Shiu
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms; D002448:Cell Adhesion / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010969:Plastics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D013873:Thionucleotides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D016376:Oligonucleotides, Antisense; D010969:Plastics; D016271:Proto-Oncogene Proteins c-myc; D013873:Thionucleotides