Cyclin E1 knockdown induces apoptosis in cancer cells
Cyclin E1 knockdown induces apoptosis in cancer cells
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DOI：
10.1179/016164106x115143
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发表时间：
2006-07-01
影响因子：
1.9
通讯作者：
Izquierdo, Marta
中科院分区：
文献类型：
--
作者：
Gurzov, Esteban N.;Izquierdo, Marta
目的：细胞周期蛋白E1在细胞周期的晚期G1期表达，并通过激活细胞周期蛋白依赖性激酶2（CDK 2）介导DNA合成的启动。异常高水平的细胞周期蛋白E1的表达经常被发现在癌细胞。方法：采用RNA干扰技术，从逆转录病毒载体中表达细胞周期蛋白E1，并在HeLa细胞、乳腺癌细胞中表达细胞周期蛋白E1。（MDA-MB-31）和胶质母细胞瘤（U-373-MG）细胞系和来自一个胶质瘤患者（GB-LP-2）的外植体。在感染后96小时，我们已经获得了非常有效的细胞周期蛋白E1蛋白的消耗（超过80%）和相当大的凋亡诱导（50-70%）。U-373-MG细胞在裸鼠中诱导肿瘤生长的能力也被取消后，细胞周期蛋白E1 knockdown.Discussion：我们的研究结果表明，逆转录病毒携带的DNA被转录成短发夹RNA（shRNA）对细胞周期蛋白E1可被用作治疗剂用于癌症治疗。
Objectives: Cyclin E1 is expressed during the late G1 phase of the cell cycle and mediates the initiation of DNA synthesis by activating cyclin-dependent kinases 2 (CDK2). Abnormally high levels of cyclin E1 expression have frequently been found in cancer cells. Here, we investigate the effect of cyclin E1 knockdown on cancer cells.Methods: RNA interference, expressed from a DNA-based retroviral vector, was used to knockdown cyclin E1 in adenocarcinoma (HeLa), breast (MDA-MB-31) and glioblastoma (U-373-MG) cell lines and an explant from one glioma patient (GB-LP-2).Results: We have obtained very efficient depletion of cyclin E1 protein (over 80%) and considerable apoptotic induction (50-70%) after 96 hours post-infection. The ability of U-373-MG cells to induce tumor growth in nude mice was also abolished after cyclin E1 knockdown.Discussion: Our results indicate that retrovirus carrying the DNA to be transcribed into a short hairpin RNA (shRNA) against cyclin E1 could be used as a therapeutic agent for cancer therapy.