Abstract
BackgroundThe 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.ResultsLow 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.ConclusionsSuppression 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.
Highlights
The aim of this work was to investigate in vitro the putative role of EGR-1 in the growth of glioma cells
EGR-1 protein was detected in normal astrocytes and in the U251 cell line stimulated with PMA [19], serving as positive control; The basal expression of EGR-1 in the U251 and two additional glioblastoma cell lines (T98G, and A172) was examined and found moderately present in all the three established glioblastoma cell lines
Densitometric measurements indicated that EGR-1 protein levels in the three positive tumor cultures were at least 20-fold lower than the level found in the unstimulated normal astrocytes, supporting the hypothesis that EGR-1 expression is downregulated in malignant tumors
Summary
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. EGR-1 is involved in the regulation of cell responses to a wide array of stimuli such as mitogens, growth factors and stress stimuli [5,6,7]. Recent studies have shown that EGR-1 expression is altered in several types of neoplasia, compared to normal tissue [1,8,9]. Later studies confirmed in two independent mouse models that EGR-1 up-regulates tumor progression [14,15]. From these various studies it is clear that EGR-1 is involved in regulation of cell proliferation
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