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Transcriptional control of the endogenous MYC protooncogene by antisense RNA

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
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A plasmid carrying antisense human MYC DNA and the gene encoding Esherichia coli xanthine/guanine phosphoribosyltransferase (Ecogpt) was introduced into human promyelocytic leukemia cell line HL-60 by protoplast fusion. High-level expression of antisense MYC RNA was obtained by selecting cells resistant to progressively higher levels of mycophenolic acid over a period of > 6 months. The constitutive production of MYC protein in clones producing high levels of antisense MYC RNA was reduced by 70% compared to parental HL-60 cells. Inhibition of MYC expression was observed not only at the translational but also at the transcriptional level, implying the antisense RNA can regulate transcription of the MYC gene. The Pst I-Pvu II fragment (920 base pairs) of the MYC leader sequence is the primary transcriptional target of the antisense RNA. The suppression of endogenous MYC gene expression by antisense RNA decreases cell proliferation and triggers monocytic differentiation.
Research Organization:
Institute of Physical and Chemical Research, Ibaraki (Japan)
OSTI ID:
6837925
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:21; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
BACTERIA
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL DIFFERENTIATION
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
DRUGS
ENZYME ACTIVITY
ENZYMES
ESCHERICHIA COLI
EVEN-ODD NUCLEI
GENE REGULATION
GENES
GLYCOSYL TRANSFERASES
HYBRIDIZATION
HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
MAMMALS
MAN
METHIONINE
MICROORGANISMS
NUCLEI
NUCLEIC ACIDS
NUCLEOTIDES
ODD-ODD NUCLEI
ONCOGENES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PENTOSYL TRANSFERASES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PLASMIDS
PRIMATES
RADIOISOTOPES
RNA
SUBCELLULAR DISTRIBUTION
SULFUR 35
SULFUR ISOTOPES
TRANSCRIPTION
TRANSFERASES
TUMOR CELLS
VERTEBRATES