Regular Article
Consequences of p53 Gene Expression by Adenovirus Vector on Cell Cycle Arrest and Apoptosis in Human Aortic Vascular Smooth Muscle Cells

https://doi.org/10.1006/bbrc.1995.2485Get rights and content

Abstract

p53 shows its tumor suppresser activity by inducing cell cycle arrest and/or apoptosis of tumor cells and these activities are in part mediated by p21 cyclin-dependent kinase inhibitor (also called as WAF1, Cip1 and SDI1). Using human aortic vascular smooth muscle cells, here we demonstrate that adenovirus vector expressing p53-induced p21, cell cycle arrest at G1 and G2/M boundary, and accumulation of cells in G1 subgroup. However, adenovirus vector expressing p21 induced only G1 cell cycle arrest. The adenovirus vector expressing p53 was 200 times more cytotoxic to human aortic vascular smooth muscle cells than adenovirus vector expressing p21. These results suggest that adenovirus expressing p53 induces cytotoxicity in human vascular smooth muscle cells by apoptosis and this cytotoxicity can not be fully accounted by p21 induction.

References (0)

Cited by (37)

  • Profound negative regulatory effects by resveratrol on vascular smooth muscle cells: A role of p53-p21<sup>WAF1/CIP1</sup> pathway

    2003, Biochemical and Biophysical Research Communications
    Citation Excerpt :

    As a chemopreventive agent against atherosclerosis, the property of resveratrol demonstrated above that it blocks cell cycle progression without inducing apoptosis at low concentrations (6.25–12.5 μM) is important. The adenovirus-mediated overexpression of p53 has been shown to be highly cytotoxic to VSMCs presumably because of the p53-mediated activation of apoptosis pathway [35]. It is likely, therefore, that the overexpression of p53 in the arterial wall by gene transfer methods would be associated with severe vascular damage due to apoptosis.

  • Decreased growth inhibitory responses of squamous carcinoma cells to interferon-γ involve failure to recruit cki proteins into cdk2 complexes

    2001, Journal of Investigative Dermatology
    Citation Excerpt :

    As all of the resistant cell lines that were used in this study are either null or mutant for p53, we examined whether the low basal levels of p21 could be related to this phenomenon. Introduction of wildtype p53 by infection with an adenovirus construct carrying p53 cDNA (Katayose et al, 1995) was able to induce the basal level of p21 in each of the SCC cell lines in a dose-dependent manner within 24 h Figure 7a, indicating that the ability of p53 to activate expression from the p21 promoter was intact in these cells. We next determined whether the presence of p53 or the resulting increase in p21 was sufficient to increase the sensitivity of the cells to IFN-γ.

  • The p53-independent tumoricidal activity of an adenoviral vector encoding a p27-p16 fusion tumor suppressor gene

    2000, Molecular Therapy
    Citation Excerpt :

    Figure 5 is a representative result; several rings were used for each experimental point and the experiment was repeated several times. Gene transfer of CDKi to tumor cells is a viable antitumor approach that has been tested by several groups (14, 15, 28–34). In a comparison of p16, p18, p19, p21, and p27, overexpression of p16, p27, and p18 was demonstrated to elicit apoptosis in tumor cells (12).

View all citing articles on Scopus
View full text