Cyclin E1 knockdown induces apoptosis in cancer cells

被引:12
作者
Gurzov, Esteban N. [1 ]
Izquierdo, Marta [1 ]
机构
[1] Univ Autonoma Madrid, Fac Ciencias, Dept Mol Biol, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain
关键词
RNA interference; cyclin E1; U-373; MG; HeLa; MDA-MB-31; cells;
D O I
10.1179/016164106X115143
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:493 / 499
页数:7
相关论文
共 20 条
[1]   Cdc2-cyclin E complexes regulate the G1/S phase transition [J].
Aleem, E ;
Kiyokawa, H ;
Kaldis, P .
NATURE CELL BIOLOGY, 2005, 7 (08) :831-U93
[2]   Predicting the future of breast cancer [J].
Borg, Å ;
Fernö, M ;
Peterson, C .
NATURE MEDICINE, 2003, 9 (01) :16-18
[3]   Induction of an interferon response by RNAi vectors in mammalian cells [J].
Bridge, AJ ;
Pebernard, S ;
Ducraux, A ;
Nicoulaz, AL ;
Iggo, R .
NATURE GENETICS, 2003, 34 (03) :263-264
[4]   Stable suppression of tumorigenicity by virus-mediated RNA interference [J].
Brummelkamp, TR ;
Bernards, R ;
Agami, R .
CANCER CELL, 2002, 2 (03) :243-247
[5]   A system for stable expression of short interfering RNAs in mammalian cells [J].
Brummelkamp, TR ;
Bernards, R ;
Agami, R .
SCIENCE, 2002, 296 (5567) :550-553
[6]   RNA interference: traveling in the cell and gaining functions? [J].
Cerutti, H .
TRENDS IN GENETICS, 2003, 19 (01) :39-46
[7]   Retrovirus-delivered siRNA [J].
Devroe E. ;
Silver P.A. .
BMC Biotechnology, 2 (1)
[8]   Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells [J].
Elbashir, SM ;
Harborth, J ;
Lendeckel, W ;
Yalcin, A ;
Weber, K ;
Tuschl, T .
NATURE, 2001, 411 (6836) :494-498
[9]   RNA interference [J].
Hannon, GJ .
NATURE, 2002, 418 (6894) :244-251
[10]  
KEYOMARSI K, 1995, ONCOGENE, V11, P941