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PMID: 3280975 Published · ppublish English Journal Article

An oligomer complementary to c-myc mRNA inhibits proliferation of HL-60 promyelocytic cells and induces differentiation.

Molecular and cellular biology ·Vol. 8 ·No. 2 ·1988-02-00 ·Pages 963-73

Holt JT, Redner RL, Nienhuis AW

Abstract

To study the role of a nuclear proto-oncogene in the regulation of cell growth and differentiation, we inhibited HL-60 c-myc expression with a complementary antisense oligomer. This oligomer was stable in culture and entered cells, forming an intracellular duplex. Incubation of cells with the anti-myc oligomer decreased the steady-state levels of c-myc protein by 50 to 80%, whereas a control oligomer did not significantly affect the c-myc protein concentration. Direct inhibition of c-myc expression with the anti-myc oligomer was associated with a decreased cell growth rate and an induction of myeloid differentiation. Related antisense oligomers with 2- to 12-base-pair mismatches with c-myc mRNA did not influence HL-60 cells. Thus, the effects of the antisense oligomer exhibited sequence specificity, and furthermore, these effects could be reversed by hybridization competition with another complementary oligomer. Antisense inhibition of a nuclear proto-oncogene apparently bypasses cell surface events in affecting cell proliferation and differentiation.

MeSH Terms
Base Sequence Cell Differentiation Cell Division Cell Line Exons Humans Leukemia, Myeloid, Acute Molecular Sequence Data Nucleic Acid Hybridization Oligodeoxyribonucleotides/chemical synthesis,isolation & purification Proto-Oncogene Mas Proto-Oncogene Proteins/analysis,genetics Proto-Oncogenes RNA, Messenger/genetics
Chemicals
MAS1 protein, human Oligodeoxyribonucleotides Proto-Oncogene Mas Proto-Oncogene Proteins RNA, Messenger
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Holt J T
Clinical Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.
Redner R L
Nienhuis A W
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.8.2.963-973.1988
Published
1988-02-00
Pages
963-73
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC363229
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.8.2.963-973.1988 PMC Full Text View journal details
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