RGD Reference Report - Down-regulation of the c-myc proto-oncogene in inhibition of vascular smooth-muscle cell proliferation: a signal for growth arrest? - Rat Genome Database

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Down-regulation of the c-myc proto-oncogene in inhibition of vascular smooth-muscle cell proliferation: a signal for growth arrest?

Authors: Bennett, MR  Littlewood, TD  Hancock, DC  Evan, GI  Newby, AC 
Citation: Bennett MR, etal., Biochem J. 1994 Sep 15;302 ( Pt 3):701-8.
RGD ID: 10059620
Pubmed: PMID:7524476   (View Abstract at PubMed)
PMCID: PMC1137288   (View Article at PubMed Central)

Vascular smooth muscle (VSM) cell proliferation contributes to the pathogenesis of atherosclerosis, restenosis after angioplasty and vein graft disease. The regulation of genes involved in VSM cell proliferation, particularly by naturally occurring inhibitors, is therefore of some importance. We have investigated the role of the c-myc proto-oncogene in growth arrest of exponentially proliferating rat VSM cells, following mitogen withdrawal, treatment with heparin (50 micrograms/ml), interferon-gamma (IFN-gamma) (100 i.u./ml), or the cyclic nucleotide analogues, 8-bromo-adenosine-3'5'-cyclic monophosphate (8-Br-cAMP; 0.1 mM) and 8-bromoguanosine-3'5'-cyclic monophosphate (8-Br-cGMP; 0.1 mM). Growth arrest was accompanied by down-regulation of c-Myc protein and mRNA following treatment with all inhibitors. Serum withdrawal or IFN-gamma treatment suppressed c-myc expression by more than 50% within 2 h, and this occurred throughout the cell cycle. Platelet-derived growth factor, epidermal growth factor and basic fibroblast growth factor all contributed independently to the maintenance of c-myc expression. Heparin, 8-Br-cAMP or 8-Br-cGMP also suppressed c-myc, but this occurred later, after 24-48 h, and was also observed following arrest by metabolic block. We conclude that c-myc expression is linked to VSM cell growth arrest in response to endogenous regulators and metabolic block. Down-regulation of c-myc expression may thus be an essential part of the arrest programme in VSM cells induced by many pharmacological agents.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Myc  (MYC proto-oncogene, bHLH transcription factor)


Additional Information