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

Wild-type p53 gene transfer inhibits neointima formation in human saphenous vein by modulation of smooth muscle cell migration and induction of apoptosis

“…21 Furthermore, in another study using human aortic SMC, overexpression of p53 was 200 times more pro-apoptotic than an adenovirus expressing p21. 19 Thus, it remains possible that human SMC derived from saphenous vein are more resistant to the growth inhibitory properties of p53 than arterial SMC, possibly through reduced susceptibility to growth inhibition, but not to apoptosis. In support of this, evidence for independent pathways regulating SMC proliferation and apoptosis in response to p53 has been documented by Bennett et al 22 There is clear evidence for the activation of multiple p53-sensitive pathways following gene transfer to SMC as demonstrated by our co-overexpression studies.…”

“…13 Other pro-death strategies have demonstrated efficacy in post-angioplasty restenosis models by overexpression of thymidine kinase. [16][17][18] Wildtype p53 (wt p53) has been shown to promote SMC apoptosis 19 and modulate SMC proliferation, 20 phenotypes that may be beneficial for prevention of neointimal hyperplasia by gene therapy. In this study we document the effect of wt p53 overexpression on human saphenous vein SMC in isolated culture and in an organ culture model of human vein graft neointimal thickening.…”

Recombinant PML adenovirus suppresses growth and tumorigenicity of human breast cancer cells by inducing G1 cell cycle arrest and apoptosis

“…There are other reports which explored the feasibility of adenovirus mediated gene transfer in breast cancer gene therapy. For example, recombinant adenovirus of p53 (Katayose et al, 1995;LesoonWood et al, 1995;Runnebaum and Kreienberg, 1995), inferferon (IFN) (Zhang et al, 1996), E1A , interleukin-2 (Su et al, 1994), herpes simplex virus thymidine kinase gene (HSV-tk) (Yee et al, 1996;Kwong et al, 1996), and Bcl-xs (Ealovega et al, 1996) have been shown to inhibit tumor growth in nude mice. Our studies presented in this report demonstrated that Ad-PML could be a much more superior gene to be used in cancer gene therapy due to the following reasons: (1) Comparatively, PML is a much more stable protein, our results demonstrated that infection of MCF-7, SK-BR-3 ( Figure 1) and prostate cancer cell lines (He et al, 1997) with Ad-PML expressed high level of PML protein and a detectable level of PML persisted for up to 16 ± 18 days post-infection.…”

“…Gene therapy could be one of the most important therapeutic approaches for treating human breast cancer in the future. In the preclinical experiments, in vivo delivery of p53 (Katayose et al, 1995;Lesoon-Wood et al, 1995;Runnebaum and Kreienberg, 1995), adenovirus type 5 early region 1A (E1A) , human interleukin-2 or interleukin-1 (Su et al, 1994), interferon (Zhang et al, 1996), Bcl-xs (Ealovega et al, 1996), and suicide gene (Yee et al, 1996;Kwong et al, 1996) have been shown to prevent/delay and suppress breast cancer growth in nude mice.…”

p21WAF1 induces permanent growth arrest and enhances differentiation, but does not alter apoptosis in PC12 cells

“…In the clonal lines described in this study, two showed no evidence of further proliferation, and in another, only rare`islands' of proliferating cells arose in the continued presence of IPTG. Overexpression of p21 has previously been shown to induce arrest (ElDeiry et al, 1993;Harper et al, 1993;Noda et al, 1994) mainly in G1, though most of these studies examined short term arrest via p21 (no more than 4 days) Katayose et al, 1995;Chen et al, 1996). Prolonged induction of p21 in other cell lines has resulted in various e ects, including apoptotic death (Sheikh et al, 1995), necrotic death (Givol et al, 1995), or decreased proliferation (not total inhibition) (Chen et al, 1995).…”