1. Inhibition of cell growth by EGR-1 in human primary cultures from malignant glioma
- Author
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Calogero, A, Lombari, V, De Gregorio, G, Porcellini, A, Ucci, S, Arcella, A, Caruso, R, Gagliardi, FM, Gulino, A, Lanzetta, G, Frati, L, Mercola, D, Ragona, G, Calogero, A., Lombari, V., Porcellini, Antonio, Arcella, A., Caruso, R., Gagliardi, F. M., Gulino, A., Frati, L., Mercol, D., and Ragona, G.
- Subjects
body regions ,lcsh:Cytology ,glioblastoma ,EGR-1 ,EGR1 ,GLIOMA-CELLS ,lcsh:QH573-671 ,Primary Research ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,hormones, hormone substitutes, and hormone antagonists - 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.
- Published
- 2004
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