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

• Main Authors: Gagliardi Franco, Caruso Riccardo, Arcella Antonietta, Ucci Severine, Porcellini Antonio, De Gregorio Giorgia, Lombari Vincenza, Calogero Antonella, Gulino Alberto, Lanzetta Gaetano, Frati Luigi, Mercola Dan, Ragona Giuseppe
• Format: Article
• Language: English
• Published: BMC 2004-01-01
• Series: Cancer Cell International
• Online Access: http://www.cancerci.com/content/4/1/1

<p>Abstract</p> <p>Background</p> <p>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 <it>p53, MDM2 </it>and <it>INK4a/ARF </it>loci, and fibronectin expression and growth characteristics were examined. A recombinant adenovirus overexpressing <it>EGR-1 </it>was tested in the primary cell lines.</p> <p>Results</p> <p>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 <it>p53 </it>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 <it>p53 </it>gene (R = 0,78, p = 0.0082). Duplication time, plating efficiency, colony formation in agarose, and contact inhibition were also altered in the <it>p53 </it>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.</p> <p>Conclusions</p> <p>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 <it>p53 </it>gene.</p>