Adenovirus 5 E1A-mediated tumor suppression associated with E1A-mediated apoptosis in vivo
Adenovirus 5 E1A-mediated tumor suppression associated with E1A-mediated apoptosis in vivo
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DOI：
10.1038/sj.onc.1202148
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发表时间：
1998-10-29
期刊：
影响因子：
8
通讯作者：
Hung, MC
中科院分区：
文献类型：
--
作者：
Deng, J;Xia, WY;Hung, MC
细胞凋亡途径的破坏是肿瘤发生的多步骤过程中的主要因素，而细胞凋亡的诱导对于肿瘤抑制和癌症治疗可能是重要的。腺病毒5型E1A基因为研究其抑瘤和凋亡功能提供了有用的工具。E1A已被证明在体外不同系统中诱导细胞凋亡。然而，这种活性尚未在体内得到很好的表征。因此，该活性的作用以及与体内生物学功能的联系尚不清楚。为了回答这些问题，我们将E1A导入小鼠黑色素瘤细胞，并在体外和体内表征其生物学特性。EIA基因的表达在体外不影响肿瘤细胞的增殖速率，但在体内抑制肿瘤生长。体外分析表明，表达E1A的肿瘤细胞对血清耗竭诱导的凋亡敏感。重要的是，E1A介导的细胞凋亡也在体内被鉴定，表明这种活性有助于肿瘤抑制功能。在体内凋亡模式是独特的：大多数凋亡细胞周围的肿瘤，暗示这些细胞与应激刺激的相互作用irvivo。此外，E1A还使肿瘤细胞对其他抗癌剂的细胞毒性敏感，这是一个有助于提高癌症治疗效果的特征。结果提供了体外活性和体内效应之间的功能联系。
Disruption of apoptotic pathways is a major factor in the multistep process of tumorigenesis, whereas induction of apoptosis can be important for tumor suppression and cancer therapy. The adenovirus type 5 E1A gene provides a useful tool to study the function of tumor suppression and apoptosis. E1A has been shown to induce apoptosis in different systems in vitro . However, this activity has not been well characterized in vivo. Therefore, the effect of this activity and the link to the in vivo biological function are not clear. To answer these questions, we introduced E1A into murine melanoma cells and characterized the biological features both in vitro and in vivo. Expression of the EIA gene does not affect the proliferation rate of tumor cells in vitro, but inhibits tumor growth in vivo. The in vitro analysis indicated that the E1A-expressing tumor cells are sensitive to serum depletion-induced apoptosis. Importantly, E1A-mediated apoptosis was also identified in vivo, suggesting this activity contributed to the tumor suppressive function. The in vivo apoptotic pattern was unique: most of the apoptotic cells were around the periphery of the tumors, implicating the interaction of these cells with stress stimuli irt vivo. In addition, E1A also rendered the tumor cells susceptible to the cytotoxicity of other anticancer agents, a feature useful for improving the efficacy of cancer therapy. The results provide a functional link between in vitro activity and in vivo effects.