Adenovirus-mediated expression of truncated E2F-1 suppresses tumor growth in vitro and in vivo.
Adenovirus-mediated expression of truncated E2F-1 suppresses tumor growth in vitro and in vivo.
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DOI：
10.1002/cncr.25322
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发表时间：
2010-09-15
期刊：
影响因子：
6.2
通讯作者：
McMasters, Kelly M.
中科院分区：
文献类型：
--
作者：
Gomez-Gutierrez, Jorge G.;Garcia-Garcia, Aracely;Hao, Hongying;Rao, Xiao-Mei;Montes de Oca-Luna, Roberto;Zhou, Heshan S.;McMasters, Kelly M.
腺病毒介导的E2 F-1基因转移在体内外均能诱导肿瘤细胞凋亡，但由于E2 F-1的致癌性，E2 F-1基因在肿瘤基因治疗中的临床应用仍存在争议。这种屏障可以通过使用E2 F-1基因（E2 Ftr）（氨基酸1至375）的截短形式来规避，该截短形式缺乏E2 F-1反式激活结构域和细胞周期促进作用。作者构建了3种在四环素（泰特）关闭系统调控下表达E2 Ftr的腺病毒载体（AdTet-E2 Ftr 1、AdTet-E2 Ftr 2和AdTet-E2 Ftr 3）。比较这些载体在癌细胞和正常细胞中的E2 Ftr表达和凋亡诱导。还在黑素瘤异种移植模型中评估了E2 Ftr体内抗肿瘤活性。其中AdTet-E2 Ftr 3表达量最高，与诱导细胞凋亡和抑制肿瘤细胞生长有关。E2 Ftr在多种癌细胞系中诱导凋亡，而与p53状态无关，在正常细胞系中具有很小的细胞毒性。在小鼠黑色素瘤异种移植模型中，与体内对照相比，AdTet-E2 Ftr 3表现出约80%的肿瘤大小减小。目前的研究结果表明，AdTet-E2 Ftr 3是一种新型的抗癌药物，在体外和体内都具有显着的治疗活性。
Adenovirus (Ad)-mediated E2F-1 gene transfer induces apoptosis in cancer cells in vitro and in vivo, but clinical application of E2F-1 in cancer gene therapy remains controversial because of the oncogenic potential of E2F-1. This barrier can be circumvented by using the truncated form of the E2F-1 gene (E2Ftr) (amino acids 1 through 375), which lacks the E2F-1 transactivation domain and cell cycle-promoting effects. The authors constructed 3 adenoviral vectors that expressed E2Ftr under regulation of the tetracycline (Tet)-off system (AdTet-E2Ftr1, AdTet-E2Ftr2, and AdTet-E2Ftr3). These vectors were compared for E2Ftr expression and apoptosis induction in cancer cells and normal cells. E2Ftr antitumor activity in vivo also was assessed in a melanoma xenograft model. One of the 3 vectors, AdTet-E2Ftr3, had the highest E2Ftr protein expression levels, which were correlated with the greatest induction of apoptosis and inhibition of cancer cell growth. E2Ftr induced apoptosis in a variety of cancer cell lines independent of p53 status with little cytotoxicity in normal cell lines. In a mouse melanoma xenograft model, AdTet-E2Ftr3 exhibited an approximately 80% decrease in tumor size compared with controls in vivo. The current results indicated that AdTet-E2Ftr3 is a novel anticancer agent that has significant therapeutic activity in vitro and in vivo.
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影响因子：
8
作者：
Bell, L. A.;O'Prey, J.;Ryan, K. M.
通讯作者：
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影响因子：
24.3
作者：
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DOI：
10.1016/j.ijrobp.2005.04.033
发表时间：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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