title: Inhibition of cell growth by EGR-1 in human primary cultures from malignant glioma.
abstract: 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.
authors.affiliation: Department of Experimental Medicine and Pathology, University of Rome "La Sapienza", Rome, 00161 Italy. antonella.calogero@uniroma1.it
authors.forename: Antonella
authors.initials: A
authors.lastname: Calogero
authors.forename: Vincenza
authors.initials: V
authors.lastname: Lombari
authors.forename: Giorgia
authors.initials: G
authors.lastname: De Gregorio
authors.forename: Antonio
authors.initials: A
authors.lastname: Porcellini
authors.forename: Severine
authors.initials: S
authors.lastname: Ucci
authors.forename: Antonietta
authors.initials: A
authors.lastname: Arcella
authors.forename: Riccardo
authors.initials: R
authors.lastname: Caruso
authors.forename: Franco Maria
authors.initials: FM
authors.lastname: Gagliardi
authors.forename: Alberto
authors.initials: A
authors.lastname: Gulino
authors.forename: Gaetano
authors.initials: G
authors.lastname: Lanzetta
authors.forename: Luigi
authors.initials: L
authors.lastname: Frati
authors.forename: Dan
authors.initials: D
authors.lastname: Mercola
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ragona