p51/p63, a novel p53 homologue, potentiates p53 activity and is a human cancer gene therapy candidate
p51/p63, a novel p53 homologue, potentiates p53 activity and is a human cancer gene therapy candidate
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DOI：
10.1002/jgm.945
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发表时间：
2006-09-01
影响因子：
3.5
通讯作者：
Tani, Kenzaburo
中科院分区：
文献类型：
--
作者：
Kunisaki, Reiko;Ikawa, Shuntaro;Tani, Kenzaburo
背景资料，第51页。(p73L/p63/p40/KET)是最近分离的一种新的P53同源物，它与P53反应元件结合，上调某些P53靶基因，并被认为与P53有部分重叠的功能。方法通过腺病毒载体将p51a基因导入人肺、胃和胰腺癌细胞，分析p51在体外和体内的抗肿瘤作用。结果p51a基因的过表达在体外均能抑制肿瘤细胞的增殖。同时携带p51和p53基因突变的EBC1细胞的锚定依赖性和独立性生长受到抑制，并且在p51和/或p53的腺病毒转导后出现明显的细胞凋亡。这种生长抑制通过联合感染同时编码p51和p53的腺病毒载体而得到协同增强。此外，p51激活了几个但不是全部的P53诱导基因，表明控制P51和P53介导的肿瘤抑制的机制不同。结论我们的观察表明，尽管与P53相比，P51的抗肿瘤作用减弱，但它协同增强了P53的抗肿瘤作用。我们的结果表明，p51在体外和体内的人癌细胞中都具有肿瘤抑制作用，可能是一种潜在的癌症基因治疗工具。版权所有(C)2006 John Wiley&Sons，Ltd.
Background p51. (p73L/p63/p40/KET), a recently isolated novel p53 homologue, binds to p53-responsive elements to upregulate some p53 target genes and has been suggested to share partially overlapping functions with p53. p51 may be a promising candidate target molecule for anti-cancer therapy.Methods In this study, we adenovirally transduced p51A cDNA into human lung, gastric and pancreatic cancer cells and analyzed the intracellular function of p51 in anti-oncogenesis in vitro and in vivo.Results Overexpression of p51A revealed an anti-proliferative effect in vitro in all the cancer cells examined in this study. The anchorage-dependent and independent cell growth of EBC1 cells carrying mutations in both p51 and p53 was suppressed and significant apoptosis following adenoviral transduction with p51 and/or p53 was seen. This growth suppression was cooperatively enhanced by the combined infection with adenoviral vectors encoding both p51 and p53. Furthermore, p51 activated several, but not all, p53-inducible genes, indicating that the mechanisms controlling p51- and p53-mediated tumor suppression differed.Conclusions Our observations indicate that, although p51 exhibited reduced anti-oncogenetic effects compared with p53, it cooperatively enhanced the anti-tumor effects of p53. Our results suggest that p51 functions as a tumor suppressor in human cancer cells in vitro and in vivo and may be useful as a potential tool for cancer gene therapy. Copyright (c) 2006 John Wiley & Sons, Ltd.