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Abstract:

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.

Registro:

Documento: Artículo
Título:Glucocorticoid-induced impairment of mammary gland involution is associated with STAT5 and STAT3 signaling modulation
Autor:Bertucci, P.Y.; Quaglino, A.; Pozzi, A.G.; Kordon, E.C.; Pecci, A.
Filiación:Inst. de Fisiol. Biologia Y Neurociencias-Consejo Nacional de Investigaciones Cientificas Y Tecnicas, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Departamento de Química Biológica, Universidad de Buenos Aires, Ciudad Universitaria, 1428 Buenos Aires, Argentina
Departamento de Fisiología, Biología Molecular Y Celular, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Departamento de Biodiversidad Y Biología Experimental, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Palabras clave: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
Año:2010
Volumen:151
Número:12
Página de inicio:5730
Página de fin:5740
DOI: http://dx.doi.org/10.1210/en.2010-0517
Título revista:Endocrinology
Título revista abreviado:Endocrinology
ISSN:00137227
CODEN:ENDOA
CAS:dexamethasone, 50-02-2; prolactin, 12585-34-1, 50647-00-2, 9002-62-4; Cytokine Receptor gp130, 133483-10-0; Dexamethasone, 50-02-2; Glucocorticoids; Il6st protein, mouse; Leukemia Inhibitory Factor; Lif protein, mouse; STAT3 Transcription Factor; STAT5 Transcription Factor; Stat3 protein, mouse; Stat5a protein, mouse
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00137227_v151_n12_p5730_Bertucci.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00137227_v151_n12_p5730_Bertucci

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Citas:

---------- APA ----------
Bertucci, P.Y., Quaglino, A., Pozzi, A.G., Kordon, E.C. & Pecci, A. (2010) . Glucocorticoid-induced impairment of mammary gland involution is associated with STAT5 and STAT3 signaling modulation. Endocrinology, 151(12), 5730-5740.
http://dx.doi.org/10.1210/en.2010-0517
---------- CHICAGO ----------
Bertucci, P.Y., Quaglino, A., Pozzi, A.G., Kordon, E.C., Pecci, A. "Glucocorticoid-induced impairment of mammary gland involution is associated with STAT5 and STAT3 signaling modulation" . Endocrinology 151, no. 12 (2010) : 5730-5740.
http://dx.doi.org/10.1210/en.2010-0517
---------- MLA ----------
Bertucci, P.Y., Quaglino, A., Pozzi, A.G., Kordon, E.C., Pecci, A. "Glucocorticoid-induced impairment of mammary gland involution is associated with STAT5 and STAT3 signaling modulation" . Endocrinology, vol. 151, no. 12, 2010, pp. 5730-5740.
http://dx.doi.org/10.1210/en.2010-0517
---------- VANCOUVER ----------
Bertucci, P.Y., Quaglino, A., Pozzi, A.G., Kordon, E.C., Pecci, A. Glucocorticoid-induced impairment of mammary gland involution is associated with STAT5 and STAT3 signaling modulation. Endocrinology. 2010;151(12):5730-5740.
http://dx.doi.org/10.1210/en.2010-0517