Inhibition of bcr-abl and/or c-abl gene expression by small interfering, double-stranded RNAs: cross-talk with cell proliferation factors and other oncogenes

Cancer
Hideki OhbaYoshinobu Baba

Abstract

Short, 21-mer, double-stranded/small interfering RNAs (ds/siRNAs) were designed to target bcr-abl mRNA in chronic myelogenous leukemia (CML) with a potential also to target c-abl mRNA. ds/siRNAs were transfected into bcr-abl-positive K-562 cells (derived from blast-crisis) or bcr-abl-negative/c-abl-positive Jurkat cells (derived from acute lymphoblastic leukemia) using lipofectamine. ds/siRNAs intracellular uptake was detected by fluorescent confocal microscopy using fluorescein-labeled ds/siRNAs. The treatment was performed over 6 days with repetitive siRNA transfections. Efficiency of the siRNAs was determined 24 hours after single siRNA transfection and 6 days after repetitive siRNA transfections. Two of the designed ds/siRNAs decreased the target mRNA levels markedly (determined by reverse transcriptase-polymerase chain reaction analysis) and bcr-abl/c-abl oncoproteins (determined by flow cytometry using Fluor-488-labeled, anti-c-abl antibody as well as by Western blot analysis). These sequences also inhibited protein tyrosine kinase activity significantly and suppressed cell proliferation. One of the three selected ds/siRNAs expressed only slight effects on the bcr-abl/c-abl mRNA in K-562 cells (but not on the oncoprotein ...Continue Reading

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Citations

Mar 21, 2006·Journal of Biomedical Science·Benjamin E BakerAlbert T Ichiki
Jul 19, 2005·Nature Biotechnology·Dieter HueskenJonathan Hall
Mar 9, 2010·Haematologica·Michael KoldehoffAhmet H Elmaagacli
Dec 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jami McLaughlinOwen N Witte
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Nov 29, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·João Miguel FreireMiguel A R B Castanho
Dec 31, 2005·Analytical Chemistry·Zhivko ZhelevYoshinobu Baba
Aug 11, 2005·Journal of the American Chemical Society·Rumiana BakalovaYoshinobu Baba

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