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腺病毒载体介导的p53基因表达对人主动脉血管平滑肌细胞细胞周期阻滞和凋亡的影响

Consequences of p53 gene expression by adenovirus vector on cell cycle arrest and apoptosis in human aortic vascular smooth muscle cells.

作者信息

Katayose D, Wersto R, Cowan K, Seth P

机构信息

Medicine Branch, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA.

出版信息

Biochem Biophys Res Commun. 1995 Oct 13;215(2):446-51. doi: 10.1006/bbrc.1995.2485.

DOI:10.1006/bbrc.1995.2485
PMID:7487976
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.

摘要

p53 通过诱导肿瘤细胞的细胞周期停滞和/或凋亡来展现其肿瘤抑制活性,并且这些活性部分由 p21 细胞周期蛋白依赖性激酶抑制剂(也称为 WAF1、Cip1 和 SDI1)介导。利用人主动脉血管平滑肌细胞,我们在此证明,表达 p53 的腺病毒载体诱导 p21 表达、细胞在 G1 期和 G2/M 边界停滞,以及细胞在 G1 亚组中积累。然而,表达 p21 的腺病毒载体仅诱导 G1 期细胞周期停滞。表达 p53 的腺病毒载体对人主动脉血管平滑肌细胞的细胞毒性比表达 p21 的腺病毒载体高 200 倍。这些结果表明,表达 p53 的腺病毒通过凋亡在人血管平滑肌细胞中诱导细胞毒性,并且这种细胞毒性不能完全由 p21 的诱导来解释。

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