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

Calogero, Antonella; Lombari, Vincenza; De Gregorio, Giorgia; Porcellini, Antonio; Ucci, Severine; Arcella, Antonietta; Caruso, Riccardo; Gagliardi, Franco Maria; Gulino, Alberto; Lanzetta, Gaetano; Frati, Luigi; Mercola, Dan; Ragona, Giuseppe

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.

GLIOMAS; TUMOR growth; P53 antioncogene; GENE expression; CELL culture; FIBRONECTINS

Cancer Cell International, 2004, Vol 4, p1

1475-2867

Academic Journal

10.1186/1475-2867-4-1