IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
artículos
Título:
Glucocorticoid alternative effects on proliferating and differentiated mammary epithelium are associated to opposite regulation of cell-cycle
Autor/es:
HOIJMAN, ESTEBAN ; ROCHA-VIEGAS, LUCIANA; KALKO, SUSANA; RUBINSTEIN, NATALIA; MORALES RUIZ, MANUEL; BAL DE KIER JOFFE E,; KORDON, EDITH C. ; PECCI, ADALI
Revista:
JOURNAL OF CELLULAR PHYSIOLOGY
Editorial:
WILEY-LISS, DIV JOHN WILEY & SONS INC
Referencias:
Año: 2012 p. 1721 - 1730
ISSN:
0021-9541
Resumen:
Glucocorticoids influence post-natal mammary gland development by sequentially controlling cell proliferation, differentiation and apoptosis. In the mammary gland, it has been demonstrated that glucocorticoid treatment inhibits epithelial apoptosis in post-lactating glands. In this study, our first goal was to identify new glucocorticoid target genes that could be involved in generating this effect. Expression profiling, by microarray analysis, revealed that expression of several cell-cycle control genes was altered by dexamethasone (DEX) treatment after lactation. Importantly, it was determined that not only the exogenous synthetic hormone, but also the endogenous glucocorticoids regulated the expression of these genes. Particularly, we found that the expression of cell cycle inhibitors, as p21CIP1 and p18INK4, was differentially regulated by glucocorticoids through the successive stages of mammary gland development. DEX treatment induced their expression and reduced cell proliferation, while in differentiated cells this hormone repressed expression of those cell cycle inhibitors and promoted survival. Therefore, differentiation status determined the effect of glucocorticoids on mammary cell fate. Particularly, we have determined that p21CIP1 inhibition would mediate the activity of these hormones in differentiated mammary cells because over-expression of this protein blocked DEX-induced apoptosis protection. Together, our data suggest that the multiple roles played by glucocorticoids in mammary gland development and function might be at least partially due to the alternative roles that these hormones play on the expression of cell cycle regulators.