Overexpression of E2F-1 in glioma triggers apoptosis and suppresses tumor growth in vitro and in vivo

被引:156
作者
Fueyo, J
Gomez-Manzano, C
Yung, WKA
Liu, TJ
Alemany, R
McDonnell, TJ
Shi, X
Rao, JS
Levin, VA
Kyritsis, AP
机构
[1] Univ Texas, MD Anderson Cancer Ctr, Dept Neurooncol, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Cancer Ctr, Dept Mol Pathol, Houston, TX 77030 USA
[3] Univ Texas, MD Anderson Cancer Ctr, Dept Neurosurg, Houston, TX 77030 USA
[4] Baxter Healthcare Corp, Unit Gene Therapy, Round Lake, IL 60073 USA
关键词
D O I
10.1038/nm0698-685
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The transfer of apoptosis genes to tumors is one of the most promising strategies for cancer gene therapy. We have shown that massive apoptosis occurs when wild-type p53 expression is induced in glioma cells carrying a p53 gene mutation. However, adenovirus-mediated p53 gene transfer is ineffective in causing apoptosis in glioma cells that retain a wild-type p53 genotype. We evaluated the effect of E2F-1 overexpression on the growth of gliomas in vitro and in vivo. In the in vitro study, the adenovirus-mediated transfer of exogenous E2F-1 protein precipitated generalized apoptosis in gliomas. The treatment with Ad5CMV-E2F-1 of nude mice carrying subcutaneous gliomas arrested tumor growth. Our results indicate that E2F-1 has anti-glioma activity in vitro and in vivo.
引用
收藏
页码:685 / 690
页数:6
相关论文
共 39 条
[1]   Complementation of helper-dependent adenoviral vectors: size effects and titer fluctuations [J].
Alemany, R ;
Dai, YF ;
Lou, YC ;
Sethi, E ;
Prokopenko, E ;
Josephs, SF ;
Zhang, WW .
JOURNAL OF VIROLOGICAL METHODS, 1997, 68 (02) :147-159
[2]  
Alemany R, 1996, CANCER GENE THER, V3, P296
[3]  
ARAP W, 1995, CANCER RES, V55, P1351
[4]  
Attia M, 1996, CANCER RES, V26, P1787
[5]  
EASTHAM JA, 1995, CANCER RES, V55, P5151
[6]   Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis [J].
Enari, M ;
Talanian, RV ;
Wong, WW ;
Nagata, S .
NATURE, 1996, 380 (6576) :723-726
[7]   E2F-1 functions in mice to promote apoptosis and suppress proliferation [J].
Field, SJ ;
Tsai, FY ;
Kuo, F ;
Zubiaga, AM ;
Kaelin, WG ;
Livingston, DM ;
Orkin, SH ;
Greenberg, ME .
CELL, 1996, 85 (04) :549-561
[8]  
Fueyo J, 1996, ONCOGENE, V12, P103
[9]  
FUEYO J, IN PRESS NEUROLOGY
[10]   Characterization of p53 and p21 functional interactions in glioma cells en route to apoptosis [J].
GomezManzano, C ;
Fueyo, J ;
Kyritsis, AP ;
McDonnell, TJ ;
Steck, PA ;
Levin, VA ;
Yung, WKA .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1997, 89 (14) :1036-1044