Suppression of bcr-abl synthesis by siRNAs or tyrosine kinase activity by Glivec alters different oncogenes, apoptotic/antiapoptotic genes and cell proliferation factors (microarray study)

FEBS Letters
Zhivko ZhelevYoshinobu Baba

Abstract

Short 21-mer double-stranded/small-interfering RNAs (ds/siRNAs) were designed to target bcr-abl mRNA in chronic myelogenous leukemia. The ds/siRNAs were transfected into bcr-abl-positive K-562 (derived from blast crisis chronic myelogenous leukemia), using lipofectamine. Penetrating of ds/siRNAs into the cells was detected by fluorescent confocal microscopy, using fluorescein-labeled ds/siRNAs. The cells were treated with mix of three siRNA sequences (3 x 60 nM) during 6 days with three repetitive transfections. The siRNA-treatment was accompanied with significant reduction of bcr-abl mRNA, p210, protein tyrosine kinase activity and cell proliferation index. Treatment of cells with Glivec (during 8 days with four repetitive doses, 180 nM single dose) resulted in analogous reduction of cell proliferation activity, stronger suppression of protein tyrosine kinase activity, and very low reduction of p210. siRNA-mix and Glivec did not affect significantly the viability of normal lymphocytes. Microarray analysis of siRNA- and Glivec-treated K-562 cells demonstrated that both pathways of bcr-abl suppression were accompanied with overexpression and suppression of many different oncogenes, apoptotic/antiapoptotic and cell proliferation ...Continue Reading

References

Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·M K MontgomeryA Fire
May 14, 1999·Current Opinion in Plant Biology·D C Baulcombe
Aug 10, 2000·Nature Biotechnology·J R Kennerdell, R W Carthew
Jan 31, 2002·Annual Review of Medicine·Michael E O'DwyerBrian J Druker
Jan 31, 2002·Proceedings of the National Academy of Sciences of the United States of America·Patrick J PaddisonGregory J Hannon
Aug 23, 2002·Pharmacology & Therapeutics·Doriano FabbroPaul W Manley
Oct 24, 2002·Blood·Michaela ScherrMatthias Eder
Dec 12, 2002·Oncogene·Richard A Van Etten
Feb 7, 2003·Current Medicinal Chemistry·Michaela ScherrMatthias Eder
Apr 16, 2003·Cell Cycle·Barbara ArdeltZbigniew Darzynkiewicz
May 30, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Laura R Saunders, Glen N Barber
Oct 31, 2003·Lancet·Nathan R Wall, Yang Shi

❮ Previous
Next ❯

Citations

Apr 5, 2005·Functional & Integrative Genomics·Hailing LiuGeoffrey Childs
Mar 21, 2006·Journal of Biomedical Science·Benjamin E BakerAlbert T Ichiki
Dec 18, 2013·Pharmacology & Therapeutics·Jianliang Zhang, Steven N Hochwald
Apr 21, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yamini ArthanariConstantinos Demonacos
May 5, 2007·Journal of Controlled Release : Official Journal of the Controlled Release Society·Toshihito TsutsumiHidetoshi Arima
May 13, 2015·Molecular Therapy. Nucleic Acids·Breanne LandryHasan Uludag
Jun 4, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Juliana Valencia-SernaHasan Uludağ
Mar 4, 2008·Molecular Cancer Research : MCR·Konrad HuppiNatasha J Caplen
Jan 6, 2010·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Mikhail DoubrovinSteven M Larson
Aug 11, 2005·Journal of the American Chemical Society·Rumiana BakalovaYoshinobu Baba

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis