Steroid drugs and GM-CSF modulate the activity of Egr-1 in glioma cells [Fármacos esteroides y el GM-CSF modulan la actividad de Egr-1 en células de glioma]
Por:
Martínez-Flores F., MacHuca-Rodríguez C., Sandoval-Zamora H., Aguirre-Cruz L., Valdez-Flores M., Villegas-Castrejón H.
Publicada:
1 ene 2013
Categoría:
Surgery
Resumen:
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, ?-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, p-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.
Filiaciones:
Martínez-Flores F.:
Laboratorio de Bioterapéutica Molecular, Instituto Nacional de Rehabilitación, Secretaría de Salud, Mexico
MacHuca-Rodríguez C.:
Laboratorio de Terapia Molecular, UMIEZ, UNAM, Mexico
Sandoval-Zamora H.:
Laboratorio de Bioterapéutica Molecular, Instituto Nacional de Rehabilitación, Secretaría de Salud, Mexico
Aguirre-Cruz L.:
Laboratorio de Neuroinmunoendocrinología, Instituto Nacional de Neurología y Neurocirugía Dr. Manuel Velazco Suárez, Secretaría de Salud, Mexico
Valdez-Flores M.:
Departamento de Genética, Instituto Nacional de Rehabilitación, Secretaría de Salud, Mexico
Villegas-Castrejón H.:
Laboratorio de Bioterapéutica Molecular, Instituto Nacional de Rehabilitación, Secretaría de Salud, Mexico
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