Glucocorticoid-induced impairment of mammary gland involution is associated with STAT5 and STAT3 signaling modulation
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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Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00137227_v151_n12_p5730_Bertucci http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00137227_v151_n12_p5730_Bertucci_oai |
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I28-R145-paper_00137227_v151_n12_p5730_Bertucci_oai2020-10-19 Bertucci, P.Y. Quaglino, A. Pozzi, A.G. Kordon, E.C. Pecci, A. 2010 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. Fil:Bertucci, P.Y. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Quaglino, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pozzi, A.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kordon, E.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pecci, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. application/pdf http://hdl.handle.net/20.500.12110/paper_00137227_v151_n12_p5730_Bertucci info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar Endocrinology 2010;151(12):5730-5740 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 Glucocorticoid-induced impairment of mammary gland involution is associated with STAT5 and STAT3 signaling modulation info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00137227_v151_n12_p5730_Bertucci_oai |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-145 |
collection |
Repositorio Digital de la Universidad de Buenos Aires (UBA) |
topic |
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 |
spellingShingle |
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 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 |
topic_facet |
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 |
description |
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. |
format |
Artículo Artículo publishedVersion |
author |
Bertucci, P.Y. Quaglino, A. Pozzi, A.G. Kordon, E.C. Pecci, A. |
author_facet |
Bertucci, P.Y. Quaglino, A. Pozzi, A.G. Kordon, E.C. Pecci, A. |
author_sort |
Bertucci, P.Y. |
title |
Glucocorticoid-induced impairment of mammary gland involution is associated with STAT5 and STAT3 signaling modulation |
title_short |
Glucocorticoid-induced impairment of mammary gland involution is associated with STAT5 and STAT3 signaling modulation |
title_full |
Glucocorticoid-induced impairment of mammary gland involution is associated with STAT5 and STAT3 signaling modulation |
title_fullStr |
Glucocorticoid-induced impairment of mammary gland involution is associated with STAT5 and STAT3 signaling modulation |
title_full_unstemmed |
Glucocorticoid-induced impairment of mammary gland involution is associated with STAT5 and STAT3 signaling modulation |
title_sort |
glucocorticoid-induced impairment of mammary gland involution is associated with stat5 and stat3 signaling modulation |
publishDate |
2010 |
url |
http://hdl.handle.net/20.500.12110/paper_00137227_v151_n12_p5730_Bertucci http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00137227_v151_n12_p5730_Bertucci_oai |
work_keys_str_mv |
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_version_ |
1766026523045789696 |