RETRACTED: Transactivation of the EGR1 gene contributes to mutant p53 gain of function (Retracted article. See vol. 79, pg. 2085, 2019)

被引:111
作者
Weisz, L [1 ]
Zalcenstein, A [1 ]
Stambolsky, P [1 ]
Cohen, Y [1 ]
Goldfinger, N [1 ]
Oren, M [1 ]
Rotter, V [1 ]
机构
[1] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel
关键词
D O I
10.1158/0008-5472.CAN-04-1145
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tumor-associated mutants of the p53 tumor suppressor protein exert biological activities compatible with an oncogenic gain of function. To explore the underlying molecular mechanism, we performed microarray analysis, comparing p53-null cells to mutant p53-expressing cells. One of the genes up-regulated in the presence of mutant p53 was EGR1, a transcription factor implicated in growth control, apoptosis, and cancer. EGR1 induction by various types of stress is markedly augmented in cells expressing mutant p53. Moreover, chromatin immunoprecipitation analysis indicates that mutant p53 is physically associated with the EGR1 promoter. Functional assays indicate that induction of EGR1 by mutant p53 contributes to enhanced transformed properties and resistance to apoptosis. We propose that EGR1 is a significant contributor to mutant p53 gain of function.
引用
收藏
页码:8318 / 8327
页数:10
相关论文
共 68 条
[1]   Impaired prostate tumorigenesis in Egr1-deficient mice [J].
Abdulkadir, SA ;
Qu, ZC ;
Garabedian, E ;
Song, SK ;
Peters, TJ ;
Svaren, J ;
Carbone, JM ;
Naughton, CK ;
Catalona, WJ ;
Ackerman, JJH ;
Gordon, JI ;
Humphrey, PA ;
Milbrandt, J .
NATURE MEDICINE, 2001, 7 (01) :101-107
[2]   Egr1 transcription factor: Multiple roles in prostate tumor cell growth and survival [J].
Adamson, ED ;
Mercola, D .
TUMOR BIOLOGY, 2002, 23 (02) :93-102
[3]  
Bae SK, 1999, CANCER RES, V59, P5989
[4]   Inhibition of Egr-1 expression reverses transformation of prostate cancer cells in vitro and in vivo [J].
Baron, V ;
De Gregorio, G ;
Krones-Herzig, A ;
Virolle, T ;
Calogero, A ;
Urcis, R ;
Mercola, D .
ONCOGENE, 2003, 22 (27) :4194-4204
[5]   p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis [J].
Bergamaschi, D ;
Gasco, M ;
Hiller, L ;
Sullivan, A ;
Syed, N ;
Trigiante, G ;
Yulug, I ;
Merlano, M ;
Numico, G ;
Comino, A ;
Attard, M ;
Reelfs, O ;
Gusterson, B ;
Bell, AK ;
Heath, V ;
Tavassoli, M ;
Farrell, PJ ;
Smith, P ;
Lu, X ;
Crook, T .
CANCER CELL, 2003, 3 (04) :387-402
[6]   Mutant p53 gain of function: differential effects of different p53 mutants on resistance of cultured cells to chemotherapy [J].
Blandino, G ;
Levine, AJ ;
Oren, M .
ONCOGENE, 1999, 18 (02) :477-485
[7]   The effects of wild-type p53 tumor suppressor activity and mutant p53 gain-of-function on cell growth [J].
Cadwell, C ;
Zambetti, GP .
GENE, 2001, 277 (1-2) :15-30
[8]  
Calogero A, 2001, CLIN CANCER RES, V7, P2788
[9]   Involvement of Egr-1/RelA synergy in distinguishing T cell activation from tumor necrosis factor-alpha-induced NF-kappa B1 transcription [J].
Cogswell, PC ;
Mayo, MW ;
Baldwin, AS .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (03) :491-497
[10]  
Deppert W, 1996, J CELL BIOCHEM, V62, P172, DOI 10.1002/(SICI)1097-4644(199608)62:2<172::AID-JCB5>3.0.CO