Inhibition of cell growth by EGR-1 in human primary cultures from malignant glioma

被引:56
作者
Calogero, Antonella [1 ,2 ]
Lombari, Vincenza [2 ]
De Gregorio, Giorgia [2 ]
Porcellini, Antonio [1 ,2 ]
Ucci, Severine [1 ]
Arcella, Antonietta [2 ]
Caruso, Riccardo [2 ,3 ]
Gagliardi, Franco Maria [2 ,3 ]
Gulino, Alberto [1 ]
Lanzetta, Gaetano [2 ,4 ]
Frati, Luigi [1 ,2 ]
Mercola, Dan [5 ,6 ]
Ragona, Giuseppe [1 ,2 ]
机构
[1] Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
[2] IRCCS Neuromed, I-86077 Pozzilli, Italy
[3] Univ Roma La Sapienza, Dept Neurol Sci, I-00161 Rome, Italy
[4] INI, I-00046 Grottaferrata, Italy
[5] Sidney Kimmel Canc Ctr, San Diego, CA 92121 USA
[6] Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA
关键词
Recombinant Adenovirus; Fibronectin Expression; Primary Cell Line; Duplication Time; Soft Agarose;
D O I
10.1186/1475-2867-4-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: The aim of this work was to investigate in vitro the putative role of EGR-1 in the growth of glioma cells. EGR-1 expression was examined during the early passages in vitro of 17 primary cell lines grown from 3 grade III and from 14 grade IV malignant astrocytoma explants. The explanted tumors were genetically characterized at the p53, MDM2 and INK4a/ARF loci, and fibronectin expression and growth characteristics were examined. A recombinant adenovirus overexpressing EGR-1 was tested in the primary cell lines. Results: Low levels of EGR-1 protein were found in all primary cultures examined, with lower values present in grade IV tumors and in cultures carrying wild-type copies of p53 gene. The levels of EGR-1 protein were significantly correlated to the amount of intracellular fibronectin, but only in tumors carrying wild-type copies of the p53 gene (R = 0,78, p = 0.0082). Duplication time, plating efficiency, colony formation in agarose, and contact inhibition were also altered in the p53 mutated tumor cultures compared to those carrying wild-type p53. Growth arrest was achieved in both types of tumor within 1-2 weeks following infection with a recombinant adenovirus overexpressing EGR-1 but not with the control adenovirus. Conclusions: Suppression of EGR-1 is a common event in gliomas and in most cases this is achieved through down-regulation of gene expression. Expression of EGR-1 by recombinant adenovirus infection almost completely abolishes the growth of tumor cells in vitro, regardless of the mutational status of the p53 gene.
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页数:12
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