pRb2/p130 promotes radiation-induced cell death in the glioblastoma cell line HJC12 by p73 upregulation and Bcl-2 downregulation

被引:17
作者
Pucci, B
Claudio, PP
Masciullo, V
Bellincampi, L
Terrinoni, A
Khalili, K
Melino, G
Giordano, A
机构
[1] Temple Univ, Sbarro Inst Canc Res & Mol Med, Coll Sci & Technol, Philadelphia, PA 19122 USA
[2] Jefferson Med Coll, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA
[3] Univ Naples Federico II, Dipartimento Sci Odontostomatol & Maxillo Faccial, I-80131 Naples, Italy
[4] Univ Roma Tor Vergata, Dipartimento Med Interna, I-00133 Rome, Italy
[5] Univ Roma Tor Vergata, Biochim Lab, IDI, IRCCS,Dipartimento Med Sperimentale & Sci Biochim, I-00133 Rome, Italy
[6] Temple Univ, Ctr Neuro Virol & Canc Biol, Philadelphia, PA 19122 USA
关键词
apoptosis; gamma-radiation; pRb2/p130; glioblastoma; p73; Bcl-2; cell cycle;
D O I
10.1038/sj.onc.1205750
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
This study shows that in the glioblastoma hamster cell line HJC12 the retinoblastoma family member pRb2/p130 enhances gamma-radiation-induced cell death. In HJC12 cells the tetracycline-regulated expression of pRb2/p130 increased the percentage of gamma-radiation-induced apoptotic cells from 27 to 47%. pRb2/p130 overexpression was associated with the downregulation of the anti-apoptotic factor Bcl-2 and the upregulation of the steady-state protein levels of the pro-apoptotic transcription factor p73. In particular, RT-PCR showed a significant increase in the expression of the p73delta isoform when pRb2/p130 was overexpressed. The ability of pRb2/p130 to modulate apoptosis was not associated with its role in mediating G0/G1 arrest during cell cycle progression. Our data suggest a role for pRb2/p130 in glioblastoma gamma-radiation-induced cell death, indicating that the antitumoral action of pRb2/p130 can regulate both inhibition of cell cycle progression and induction of cell death.
引用
收藏
页码:5897 / 5905
页数:9
相关论文
共 48 条
[1]  
Agami R, 1999, NATURE, V399, P809
[2]  
An B, 1996, CANCER RES, V56, P438
[3]   THE RB2/P130 GENE-PRODUCT IS A NUCLEAR-PROTEIN WHOSE PHOSPHORYLATION IS CELL-CYCLE-REGULATED [J].
BALDI, A ;
DELUCA, A ;
CLAUDIO, PP ;
BALDI, F ;
GIORDANO, GG ;
TOMMASINO, M ;
PAGGI, MG ;
GIORDANO, A .
JOURNAL OF CELLULAR BIOCHEMISTRY, 1995, 59 (03) :402-408
[4]  
Berry DE, 1996, ONCOGENE, V12, P1809
[5]  
Bowen C, 1998, CANCER RES, V58, P3275
[6]  
CHOISYROSSI C, 1999, CELL DEATH DIFFER, V5, P1162
[7]  
Claudio PP, 2000, CANCER RES, V60, P372
[8]  
CLAUDIO PP, 1994, CANCER RES, V54, P5555
[9]   Shared role of the pRB-related p130 and p107 proteins in limb development [J].
Cobrinik, D ;
Lee, MH ;
Hannon, G ;
Mulligan, G ;
Bronson, RT ;
Dyson, N ;
Harlow, E ;
Beach, D ;
Weinberg, RA ;
Jacks, T .
GENES & DEVELOPMENT, 1996, 10 (13) :1633-1644
[10]   FEATURES OF APOPTOTIC CELLS MEASURED BY FLOW-CYTOMETRY [J].
DARZYNKIEWICZ, Z ;
BRUNO, S ;
DELBINO, G ;
GORCZYCA, W ;
HOTZ, MA ;
LASSOTA, P ;
TRAGANOS, F .
CYTOMETRY, 1992, 13 (08) :795-808