Expression of c-myc is not critical for cell proliferation in established human leukemia lines



Tidd, David M, Giles, Richard V, Broughton, Caroline M and Clark, Richard E
(2001) Expression of c-myc is not critical for cell proliferation in established human leukemia lines. BMC Molecular Biology, 2.

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Abstract

Background: A study was undertaken to resolve preliminary conflicting results on the proliferation of leukemia cells observed with different c-myc antisense oligonucleotides. Results: RNase H-active, chimeric methylphosphonodiester / phosphodiester antisense oligodeoxynucleotides targeting bases 1147–1166 of c-myc mRNA downregulated c-Myc protein and induced apoptosis and cell cycle arrest respectively in cultures of MOLT-4 and KYO1 human leukemia cells. In contrast, an RNase H-inactive, morpholino antisense oligonucleotide analogue 28-mer, simultaneously targeting the exon 2 splice acceptor site and initiation codon, reduced c- Myc protein to barely detectable levels but did not affect cell proliferation in these or other leukemia lines. The RNase H-active oligodeoxynucleotide 20-mers contained the phosphodiester linked motif CGTTG, which as an apoptosis inducing CpG oligodeoxynucleotide 5-mer of sequence type CGNNN (N = A, G, C, or T) had potent activity against MOLT-4 cells. The 5-mer mimicked the antiproliferative effects of the 20-mer in the absence of any antisense activity against c-myc mRNA, while the latter still reduced expression of c-myc in a subline of MOLT-4 cells that had been selected for resistance to CGTTA, but in this case the oligodeoxynucleotide failed to induce apoptosis or cell cycle arrest. Conclusions: We conclude that the biological activity of the chimeric c-myc antisense 20-mers resulted from a non-antisense mechanism related to the CGTTG motif contained within the sequence, and not through downregulation of c-myc. Although the oncogene may have been implicated in the etiology of the original leukemias, expression of c-myc is apparently no longer required to sustain continuous cell proliferation in these culture lines.

Item Type: Article
Additional Information: Published: 16 November 2001.
Uncontrolled Keywords: leukemia cells, c-myc antisense oligonucleotides
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: ?? dep_biosci ??
Depositing User: Symplectic Admin
Date Deposited: 07 Jul 2008 15:28
Last Modified: 09 Jan 2021 08:59
DOI: 10.1186/1471-2199-2-13
Publisher's Statement : © 2001 Tidd et al; licensee BioMed Central Ltd. Verbatim copying and redistribution of this article are permitted in any medium for any non-commercial purpose, provided this notice is preserved along with the article's original URL. For commercial use, contact info@biomedcentral.com. This article is available from: http://www.biomedcentral.com/1471-2199/2/13
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URI: https://livrepository.liverpool.ac.uk/id/eprint/799