Inhibition of cell growth by EGR-1 in human primary cultures from malignant glioma
被引:56
作者:
Calogero, Antonella
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Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
IRCCS Neuromed, I-86077 Pozzilli, ItalyUniv Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
Calogero, Antonella
[1
,2
]
Lombari, Vincenza
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IRCCS Neuromed, I-86077 Pozzilli, ItalyUniv Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
Lombari, Vincenza
[2
]
De Gregorio, Giorgia
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IRCCS Neuromed, I-86077 Pozzilli, ItalyUniv Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
De Gregorio, Giorgia
[2
]
Porcellini, Antonio
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Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
IRCCS Neuromed, I-86077 Pozzilli, ItalyUniv Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
Porcellini, Antonio
[1
,2
]
Ucci, Severine
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Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, ItalyUniv Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
Ucci, Severine
[1
]
Arcella, Antonietta
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IRCCS Neuromed, I-86077 Pozzilli, ItalyUniv Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
Arcella, Antonietta
[2
]
Caruso, Riccardo
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IRCCS Neuromed, I-86077 Pozzilli, Italy
Univ Roma La Sapienza, Dept Neurol Sci, I-00161 Rome, ItalyUniv Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
Caruso, Riccardo
[2
,3
]
Gagliardi, Franco Maria
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IRCCS Neuromed, I-86077 Pozzilli, Italy
Univ Roma La Sapienza, Dept Neurol Sci, I-00161 Rome, ItalyUniv Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
Gagliardi, Franco Maria
[2
,3
]
Gulino, Alberto
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Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, ItalyUniv Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
Gulino, Alberto
[1
]
Lanzetta, Gaetano
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IRCCS Neuromed, I-86077 Pozzilli, Italy
INI, I-00046 Grottaferrata, ItalyUniv Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
Lanzetta, Gaetano
[2
,4
]
Frati, Luigi
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机构:
Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
IRCCS Neuromed, I-86077 Pozzilli, ItalyUniv Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
Frati, Luigi
[1
,2
]
Mercola, Dan
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机构:
Sidney Kimmel Canc Ctr, San Diego, CA 92121 USA
Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USAUniv Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
Mercola, Dan
[5
,6
]
Ragona, Giuseppe
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机构:
Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
IRCCS Neuromed, I-86077 Pozzilli, ItalyUniv Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
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
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.