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

DOI: 10.1186/1475-2867-4-1

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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.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.EGR-1 encodes a nuclear phosphoprotein that binds to DNA and regulates transcription through a GC-rich consensus sequence [1-4]. EGR-1 is involved in the regulation of cell responses to a wide array of stimuli such as mitogens, growth factors and stress stimuli [5-7]. Recent studies have shown that EGR-1 expression is altered in several types of neoplasia, compared to normal tissue [1,8,9]. Gene deletion or EGR-1 mutations have been reported in sporadic hematological malignancies [10]. EGR-1 expression has been found to be either decreased or undetectable in human breast cancer tissue and small cell lung carcinoma [11,12]. EGR-1 is altered in a different manner in prostate cancer, where higher levels of EGR-1 expression are found correlated to more advanced stages of malignancy [13]. 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


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