[Steroid drugs and GM-CSF modulates activity of Egr-1 in glioma cells]. / Fármacos esteroides y el GM-CSF modulan la actividad de Egr-1 en células de glioma.

INTRODUCTION: The Egr-1 protein is a transcriptional factor responsive to early growth. Transcriptional regulation of the promoter has been described like responsive to physical stress, osmotic changes, and cellular growth marker. However, there is no report about the pharmacological effect on the transcriptional regulation in gliomas. Hereby we report the modulation of the Egr-1 promoter transcriptional activity induced by the Granulocytes Macrophages Colony Stimulating Factor (GM-CSF) and steroid drugs in human glioma cells (CH235-GM Grade II, U373-GM Grade III, D54-GM Grade IV) using a reporter system transduced by a recombinant adenoviral vector AdEgr-1/luc7. METHODS: Human glioma cells shows with different malignity grade (CH235-GM Grado II; U373-GM Grado III; D54-GM Grado IV) were transduced with no replicative adenoviral vector AdEgr-1/Luc7 and exposed to drugs as progesterone, ß-estradiol and betametasone, and GM-CSF. Transcriptional activity of the egr-1 promoter was quantified by Luciferase reporter gene, cloned downstream to the tata box. Luciferase activity was quantified from whole cell proteins using luminometry assays. RESULTS: U373-GM cell line with GM-CSF, shows an increment on transcriptional activity of Egr-1 promoter, also in endogen way. U373-GM showed a positive regulation of Egr-1, with steroid drugs on the times analyzed. Steroid drugs as progesterone, ß-estradiol and betametasone, shows a pleiotropic behavior on CH235-GM and D54-GM, glioma cell lines. CONCLUSIONS: Inhibition or activation response of Egr-1 promoter shows new framework to explore a mechanism of action of steroid drugs on genetic and epigenetic regulation on tumoral process.

NF-kappaB activation but not PI3K/Akt is required for dexamethasone dependent protection against TNF-alpha cytotoxicity in L929 cells.

Tumor necrosis factor alpha (TNF-alpha) is one of the best-described cell death promoters. In murine L929 fibroblasts, dexamethasone inhibits TNF-alpha-induced cytotoxicity. Since phosphatidyl inositol 3 kinase (PI3K) and nuclear factor kappa B (NF-kappaB) proteins regulate several survival pathways, we evaluated their participation in dexamethasone protection against TNF-alpha cell death. We interfered with these pathways by overexpressing a negative dominant mutant of PI3K or a non-degradable mutant of inhibitor of NF-kappaB alpha (IkappaBalpha) (the cytoplasmic inhibitor of NF-kappaB) in L929 cells. The mutant IkappaB, but not the mutant PI3K, abrogated dexamethasone-mediated protection. The loss of dexamethasone protection was associated with a diminished accumulation in XIAP and c-IAP proteins.