Glucocorticoid differential effects on p21CIP1 expression, cell cycle and survival of mammary cells

HOIJMAN, E.; PECCI A.

Villa Carlos Paz, Córdoba

Congreso; XLIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2008

SAIB

Glucocorticoid administration prevents post-lactation mammary gland involution, including apoptosis of mammary epithelial cells. By microarray analysis, we previously identified glucocorticoid regulated genes involved in the in vivo antiapoptotic action. Several genes are downregulated upon the hormone treatment, as the cell cycle inhibitors p21CIP1 and p18INK4c. In order to evaluate wether glucocorticoids regulate these genes by acting directly on mammary epithelial cells, we analyzed their mRNA levels by real-time PCR in mammary gland whole organ culture and in the normal mammary epithelial cell line, HC11. Dexamethasone treatment regulated the expression levels of these genes in both experimental systems. Interestingly, while glucocorticoids repress p21CIP1 and p18INK4c expression in HC11 differentiated cells, they increase the mRNA levels of these genes when the cells are undifferentiated. This differential effect was also observed at the cellular level: dexamethasone prevents apoptosis (Caspase-3 activity) induced by hormone removal of HC11 differentiated cells, but it induce cell cycle arrest (DNA content by flow cytometry) on undifferentiated cells. The differential response was also observed on mammary cells in vivo. Thus, gene expression regulation by glucocorticoids in mammary gland is dependent on cellular context, and could in turn determine the cellular outcome.