Abstract:
:We have investigated the requirement for c-myc downregulation in the growth arrest of vascular smooth muscle cells (VSMCs). Rat VSMCs were infected with a retrovirus vector directing constitutive expression of either the complete human c-Myc protein (VSM-myc cells) or the c-Myc deletion mutant D106-143, which is inactive in cotransformation and autosuppression assays (VSM-D106-143 myc cells). Clones of transfected VSM-myc cells were isolated that constitutively expressed a range of levels of c-Myc protein from that observed in normal proliferating VSMCs to approximately seven times normal. The growth rates of these clones and their responses to growth inhibitors were then assessed. VSM-myc clones possessed a shorter mean intermitotic time than normal cells, which was inversely correlated (P < .05) with the level of c-Myc protein expressed. VSM-myc cells also expressed lower levels of alpha-smooth muscle actin mRNA and protein and exhibited an altered morphology. The proliferation of normal VSMCs and VSM-D106-143 myc cells was inhibited by serum reduction (0.5% fetal calf serum) and also by treatment with interferon-gamma (100 IU/mL), heparin (50 micrograms/mL), 8-bromo-cAMP (0.1 mmol/L), or 8-bromo-cGMP (0.1 mmol/L). In contrast, proliferation of VSM-myc cells was not inhibited by any of these agents, even if present at 10-fold higher concentrations. However, approximately 75% of VSM-myc cells expressing levels of c-Myc protein seen in normal proliferating VSMCs underwent apoptosis after 4 days of serum reduction or treatment with interferon-gamma. The results show that constitutive c-myc expression induces continuous cell proliferation, reduction in alpha-smooth muscle actin expression and apoptosis in VSMCs. We conclude that downregulation of c-myc is a prerequisite for growth arrest and subsequent survival of VSMCs. Conversely, deregulated c-myc expression may be important in the proliferation and death of VSMCs--characteristics of the pathogenesis of atherosclerosis.
journal_name
Circ Resjournal_title
Circulation researchauthors
Bennett MR,Evan GI,Newby ACdoi
10.1161/01.res.74.3.525subject
Has Abstractpub_date
1994-03-01 00:00:00pages
525-36issue
3eissn
0009-7330issn
1524-4571journal_volume
74pub_type
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更新日期:2009-01-02 00:00:00
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更新日期:1990-08-01 00:00:00
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更新日期:2007-03-02 00:00:00
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更新日期:1975-06-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2017-02-03 00:00:00
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更新日期:2015-08-28 00:00:00
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更新日期:1995-02-01 00:00:00
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pub_type: 杂志文章,随机对照试验
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更新日期:2019-05-10 00:00:00
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更新日期:1980-11-01 00:00:00