Glucocorticoid-induced impairment of mammary gland involution is associated with STAT5 and STAT3 signaling modulation

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The mammary epithelium undergoes cyclical periods of cellular proliferation, differentiation, and regression. During lactation, the signal transducer and activator of transcription factor (STAT)-5A and the glucocorticoid receptor (GR) synergize to induce milk protein expression and also act as survi...

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Detalles Bibliográficos
Autores principales: Bertucci, P.Y., Quaglino, A., Pozzi, A.G., Kordon, E.C., Pecci, A.
Formato: Artículo publishedVersion
Publicado: 2010
Materias:
beta casein
dexamethasone
glucocorticoid
prolactin
STAT3 protein
STAT5 protein
animal experiment
animal tissue
apoptosis
article
down regulation
epithelium cell
extracellular matrix
gene expression
mammary gland
mouse
nonhuman
priority journal
protein degradation
signal transduction
weaning
Animals
Cytokine Receptor gp130
Dexamethasone
DNA Fragmentation
Female
Gene Expression Regulation
Glucocorticoids
Lactation
Leukemia Inhibitory Factor
Mammary Glands, Animal
Mice
Mice, Inbred BALB C
Signal Transduction
STAT3 Transcription Factor
STAT5 Transcription Factor
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00137227_v151_n12_p5730_Bertucci
https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00137227_v151_n12_p5730_Bertucci_oai
Aporte de:
Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
Descripción
Sumario:The mammary epithelium undergoes cyclical periods of cellular proliferation, differentiation, and regression. During lactation, the signal transducer and activator of transcription factor (STAT)-5A and the glucocorticoid receptor (GR) synergize to induce milk protein expression and also act as survival factors. During involution, STAT3 activation mediates epithelial cell apoptosis and mammary gland remodeling. It has been shown that the administration of glucocorticoids at weaning prevents epithelial cell death, probably by extracellular matrix breakdown prevention. Our results show that the synthetic glucocorticoid dexamethasone (DEX) modulates STAT5A and STAT3 signaling and inhibits apoptosis induction in postlactating mouse mammary glands, only when administered within the first 48 h upon cessation of suckling. DEX administration right after weaning delayed STAT5A inactivation and degradation, preserving gene expression of target genes as β-casein (bcas) and prolactin induced protein (pip). Weaning-triggered GR down-regulation is also delayed by the hormone treatment. Moreover, DEX administration delayed STAT3 activation and translocation into epithelial cells nuclei. In particular, DEX treatment impaired the increment in gene expression of signal transducer subunit gp130, normally up-regulated from lactation to involution and responsible for STAT3 activation. Therefore, the data shown herein indicate that glucocorticoids are able to modulate early involution by controlling the strong cross talk that GR, STAT5, and STAT3 pathways maintains in the mammary epithelium. Copyright © 2010 by The Endocrine Society.

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