Adenovirus-mediated transfer of the p53 family genes, p73 and p51/p63 induces cell cycle arrest and apoptosis in colorectal cancer cell lines: potential application to gene therapy of colorectal cancer
Adenovirus-mediated transfer of the p53 family genes, p73 and p51/p63 induces cell cycle arrest and apoptosis in colorectal cancer cell lines: potential application to gene therapy of colorectal cancer
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DOI：
10.1038/sj.gt.3301538
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发表时间：
2001-09
期刊：
影响因子：
5.1
通讯作者：
Y. Sasaki;I. Morimoto;S. Ishida;T. Yamashita;K. Imai;T. Tokino
中科院分区：
文献类型：
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作者：
Y. Sasaki;I. Morimoto;S. Ishida;T. Yamashita;K. Imai;T. Tokino
P53基因疗法正在临床试验中用于治疗人类癌症，然而，一些癌症模型（体内和体外）对P53有抗药性。为了探索p53的两个同源物p73和p51/p63在癌症基因治疗中的潜在应用，我们通过腺病毒载体将p53、p73和p51/p63导入结直肠癌细胞系，并比较它们对细胞生长的影响。在测试的10个细胞系中，6个细胞系在p53、p73β或p51A/p63γ转导后表现出类似的反应；2株细胞周期阻滞，3株细胞凋亡，1株无影响。对细胞周期进程的影响在其他四种细胞系中是可变的。有趣的是，三种细胞系对p53介导的凋亡具有抗性，包括两种内源性野生型p53等位基因的细胞系，但在p73β或p51A/p63γ转导后发生凋亡。与p53类似，p51A/p63γ的转导在阿霉素或x射线联合作用下可诱导SW480细胞广泛凋亡，而SW480细胞通常对凋亡具有抗性。p73β和p51A/p63γ的转导也降低了体内两种结直肠癌细胞的致瘤性。这些结果表明，腺病毒介导的p73β和p51A/p63γ转移是治疗人类癌症的潜在新途径，特别是对p53基因治疗耐药的肿瘤。基因治疗（2001）8,1401 - 1408。
p53 gene therapy is being tested clinically for the treatment of human cancer, however, some cancer models (in vivo and in vitro) are resistant to p53. To explore the potential use of two p53 homologues, p73 and p51/p63, in cancer gene therapy, we introduced p53, p73 and p51/p63 into colorectal cancer cell lines via adenoviral vectors, and compared their effects on cell growth. Among 10 cell lines tested, six cell lines displayed a similar response following transduction of p53, p73β or p51A/p63γ; two lines underwent cell-cycle arrest, three lines exhibited apoptosis and one line showed no-effect following transduction. The effect on cell-cycle progression was variable in the other four cell lines. Interestingly, three cell lines were resistant to p53-mediated apoptosis, including two lines having endogenous wild-type p53 alleles, but underwent apoptosis after transduction of p73β or p51A/p63γ. Similar to p53, transduction of p51A/p63γ induced extensive apoptosis when combined with adriamycin or X-radiation in SW480 cells, which are normally resistant to apoptosis. Transduction of p73β and p51A/p63γ also reduced the tumorigenicity of two colorectal cancer cells in vivo. These results suggest that adenovirus-mediated p73β and p51A/p63γ transfer are potential novel approaches for the treatment of human cancers, particularly for tumors that are resistant to p53 gene therapy. Gene Therapy (2001) 8, 1401–1408.