INICSA   23916
INSTITUTO DE INVESTIGACIONES EN CIENCIAS DE LA SALUD
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Modifications in satatus methylation of global DNA and p53 and p21 gene promoters during the development of experimental pituitary tumors
Autor/es:
DA SILVA R.; TORRES, A I; SABATINO M E; SOSA L DEL V.; LATINI, A; GRONDONA E; DE PAUL, A L
Lugar:
Praga
Reunión:
Congreso; 12th International Congress of Cell Biology; 2016
Institución organizadora:
Czech Society for Cell Biology
Resumen:
Global and gene-specific changes to the epigenome are hallmarks of most tumors including those of pituitary origin, and this fact might offer important details about changes observed in the genesis and development tumural. The objective of this work was evaluate the epigenetic variations associated to development of experimental tumoral pituitary induced by estrogen. The pituitaries of estrogenized male rats after 10, 20, 40 and 60 days were processed for sequential DNA and RNA co-extraction. The global DNA methylation was analyze by with MspI/HpaII endonucleases and DNMT1, DNMT3A and DNMT3B, TETs family enzymes, 8-oxiguanine DNA glycosylase 1 (OGG-1) and B-actin mRNA expression were determine by semiquantitative RT-PCR. The promoter methylation for P53 and P21 was carried out by methylation-sensitive restriction enzymes. To assess DMNT 1 localization from different experimental conditions were processed for epifluorescence microscopy and DMNT 1 protein expression was analyze by WB. Statistics: ANOVA-Fisher. The global hypomethylation was observed from 20 to 60 days of estrogen stimulation correlate to a decrease of DNMT1 protein expression, loss of nuclear localization and mRNA diminution detected at 60d. Moreover, the mRNA expression of DNMT3A and DNMT3B and TETs family enzymes were not modified. The OGG-1 gene expression increased during all time of estrogen treatment. Finally, a focal hypermethylation in regulatory cell cycle, p53 and p21, genes was observed at 20d and 60d. Our findings show a failure of maintenance methylation by the DNA methyltransferase, DNMT1; DNA damage and an inhibition in proliferative regulators leading to phenotype observed during pituitary tumor development