p42/p44 MAPK-mediated Stat3 Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth

Autores
Tkach, Mercedes; Rosemblit, Cinthia; Rivas, Martin Alfredo; Proietti Anastasi, Cecilia Jazmín; Díaz Flaqué, María Celeste; Mercogliano, María Florencia; Beguelin, Wendy; Maronna, Esteban; Guzman, Pablo; Gercovich, Felipe G.; Gil Deza, Ernesto; Elizalde, Patricia Virginia; Schillaci, Roxana
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Stat3 is a signaling node for multiple oncogenic pathways and is therefore frequently active in breast cancer. As experimental and clinical evidence reveals that progestins are key players in controlling mammary gland tumorigenesis, we studied Stat3 participation in this event. We have previously shown that progestins induce Stat3Tyr705 phosphorylation and its transcriptional activation in breast cancer cells. In this study, we demonstrate that progestins also induce Stat3 phosphorylation at Ser727 residue, which occurs via activation of c-Src/p42/p44 MAPK pathways in murine progestin-dependent C4HD cells and in T-47D cells. Expression of a Stat3S727A vector, which carries a serine-to-alanine substitution at codon 727, shows that Stat3Ser727 phosphorylation is required for full transcriptional activation of cyclin D1 gene expression by progestins and for in vivo Stat3 recruitment on cyclin D1 promoter. Transfection of Stat3S727A in murine and human breast cancer cells abolished progestin-induced in vitro and in vivo growth. Moreover, we found a positive correlation between progesterone receptor expression and nuclear localization of Stat3Ser727 phosphorylation in breast cancer biopsies. These data highlight Stat3 phosphorylation in Ser727 residue as a nongenomic action by progestins, necessary to promote breast cancer growth.
Fil: Tkach, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Rosemblit, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Rivas, Martin Alfredo. Vall d; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Proietti Anastasi, Cecilia Jazmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Díaz Flaqué, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Mercogliano, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Beguelin, Wendy. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Maronna, Esteban. Sanatorio Mater Dei; Argentina
Fil: Guzman, Pablo. Universidad de la Frontera. Facultad de Medicina; Chile
Fil: Gercovich, Felipe G.. Instituto Oncológico Henry Moore; Argentina
Fil: Gil Deza, Ernesto. Instituto Oncológico Henry Moore; Argentina
Fil: Elizalde, Patricia Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Schillaci, Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Materia
STAT3
PROGESTIN
BREAST CANCER
P42/P44 MAPK
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/5548
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/5548
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling p42/p44 MAPK-mediated Stat3 Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growthTkach, MercedesRosemblit, CinthiaRivas, Martin AlfredoProietti Anastasi, Cecilia JazmínDíaz Flaqué, María CelesteMercogliano, María FlorenciaBeguelin, WendyMaronna, EstebanGuzman, PabloGercovich, Felipe G.Gil Deza, ErnestoElizalde, Patricia VirginiaSchillaci, RoxanaSTAT3PROGESTINBREAST CANCERP42/P44 MAPKhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Stat3 is a signaling node for multiple oncogenic pathways and is therefore frequently active in breast cancer. As experimental and clinical evidence reveals that progestins are key players in controlling mammary gland tumorigenesis, we studied Stat3 participation in this event. We have previously shown that progestins induce Stat3Tyr705 phosphorylation and its transcriptional activation in breast cancer cells. In this study, we demonstrate that progestins also induce Stat3 phosphorylation at Ser727 residue, which occurs via activation of c-Src/p42/p44 MAPK pathways in murine progestin-dependent C4HD cells and in T-47D cells. Expression of a Stat3S727A vector, which carries a serine-to-alanine substitution at codon 727, shows that Stat3Ser727 phosphorylation is required for full transcriptional activation of cyclin D1 gene expression by progestins and for in vivo Stat3 recruitment on cyclin D1 promoter. Transfection of Stat3S727A in murine and human breast cancer cells abolished progestin-induced in vitro and in vivo growth. Moreover, we found a positive correlation between progesterone receptor expression and nuclear localization of Stat3Ser727 phosphorylation in breast cancer biopsies. These data highlight Stat3 phosphorylation in Ser727 residue as a nongenomic action by progestins, necessary to promote breast cancer growth.Fil: Tkach, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Rosemblit, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Rivas, Martin Alfredo. Vall d; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Proietti Anastasi, Cecilia Jazmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Díaz Flaqué, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Mercogliano, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Beguelin, Wendy. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Maronna, Esteban. Sanatorio Mater Dei; ArgentinaFil: Guzman, Pablo. Universidad de la Frontera. Facultad de Medicina; ChileFil: Gercovich, Felipe G.. Instituto Oncológico Henry Moore; ArgentinaFil: Gil Deza, Ernesto. Instituto Oncológico Henry Moore; ArgentinaFil: Elizalde, Patricia Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Schillaci, Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaBioscientifica2013-03-22info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/mswordhttp://hdl.handle.net/11336/5548Tkach, Mercedes; Rosemblit, Cinthia; Rivas, Martin Alfredo; Proietti Anastasi, Cecilia Jazmín; Díaz Flaqué, María Celeste; et al.; p42/p44 MAPK-mediated Stat3 Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth; Bioscientifica; Endocrine - Related Cancer; 20; 2; 22-3-2013; 197-2121351-00881479-6821enginfo:eu-repo/semantics/altIdentifier/ark/10.1530/ERC-12-0194info:eu-repo/semantics/altIdentifier/pmid/23329648info:eu-repo/semantics/altIdentifier/url/http://erc.endocrinology-journals.org/content/20/2/197.longinfo:eu-repo/semantics/altIdentifier/doi/10.1530/ERC-12-0194info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-03-31T15:22:06Zoai:ri.conicet.gov.ar:11336/5548instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-03-31 15:22:06.422CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv p42/p44 MAPK-mediated Stat3 Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth
title p42/p44 MAPK-mediated Stat3 Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth
spellingShingle p42/p44 MAPK-mediated Stat3 Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth
Tkach, Mercedes
STAT3
PROGESTIN
BREAST CANCER
P42/P44 MAPK
title_short p42/p44 MAPK-mediated Stat3 Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth
title_full p42/p44 MAPK-mediated Stat3 Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth
title_fullStr p42/p44 MAPK-mediated Stat3 Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth
title_full_unstemmed p42/p44 MAPK-mediated Stat3 Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth
title_sort p42/p44 MAPK-mediated Stat3 Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth
dc.creator.none.fl_str_mv Tkach, Mercedes
Rosemblit, Cinthia
Rivas, Martin Alfredo
Proietti Anastasi, Cecilia Jazmín
Díaz Flaqué, María Celeste
Mercogliano, María Florencia
Beguelin, Wendy
Maronna, Esteban
Guzman, Pablo
Gercovich, Felipe G.
Gil Deza, Ernesto
Elizalde, Patricia Virginia
Schillaci, Roxana
author Tkach, Mercedes
author_facet Tkach, Mercedes
Rosemblit, Cinthia
Rivas, Martin Alfredo
Proietti Anastasi, Cecilia Jazmín
Díaz Flaqué, María Celeste
Mercogliano, María Florencia
Beguelin, Wendy
Maronna, Esteban
Guzman, Pablo
Gercovich, Felipe G.
Gil Deza, Ernesto
Elizalde, Patricia Virginia
Schillaci, Roxana
author_role author
author2 Rosemblit, Cinthia
Rivas, Martin Alfredo
Proietti Anastasi, Cecilia Jazmín
Díaz Flaqué, María Celeste
Mercogliano, María Florencia
Beguelin, Wendy
Maronna, Esteban
Guzman, Pablo
Gercovich, Felipe G.
Gil Deza, Ernesto
Elizalde, Patricia Virginia
Schillaci, Roxana
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv STAT3
PROGESTIN
BREAST CANCER
P42/P44 MAPK
topic STAT3
PROGESTIN
BREAST CANCER
P42/P44 MAPK
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Stat3 is a signaling node for multiple oncogenic pathways and is therefore frequently active in breast cancer. As experimental and clinical evidence reveals that progestins are key players in controlling mammary gland tumorigenesis, we studied Stat3 participation in this event. We have previously shown that progestins induce Stat3Tyr705 phosphorylation and its transcriptional activation in breast cancer cells. In this study, we demonstrate that progestins also induce Stat3 phosphorylation at Ser727 residue, which occurs via activation of c-Src/p42/p44 MAPK pathways in murine progestin-dependent C4HD cells and in T-47D cells. Expression of a Stat3S727A vector, which carries a serine-to-alanine substitution at codon 727, shows that Stat3Ser727 phosphorylation is required for full transcriptional activation of cyclin D1 gene expression by progestins and for in vivo Stat3 recruitment on cyclin D1 promoter. Transfection of Stat3S727A in murine and human breast cancer cells abolished progestin-induced in vitro and in vivo growth. Moreover, we found a positive correlation between progesterone receptor expression and nuclear localization of Stat3Ser727 phosphorylation in breast cancer biopsies. These data highlight Stat3 phosphorylation in Ser727 residue as a nongenomic action by progestins, necessary to promote breast cancer growth.
Fil: Tkach, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Rosemblit, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Rivas, Martin Alfredo. Vall d; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Proietti Anastasi, Cecilia Jazmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Díaz Flaqué, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Mercogliano, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Beguelin, Wendy. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Maronna, Esteban. Sanatorio Mater Dei; Argentina
Fil: Guzman, Pablo. Universidad de la Frontera. Facultad de Medicina; Chile
Fil: Gercovich, Felipe G.. Instituto Oncológico Henry Moore; Argentina
Fil: Gil Deza, Ernesto. Instituto Oncológico Henry Moore; Argentina
Fil: Elizalde, Patricia Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Schillaci, Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
description Stat3 is a signaling node for multiple oncogenic pathways and is therefore frequently active in breast cancer. As experimental and clinical evidence reveals that progestins are key players in controlling mammary gland tumorigenesis, we studied Stat3 participation in this event. We have previously shown that progestins induce Stat3Tyr705 phosphorylation and its transcriptional activation in breast cancer cells. In this study, we demonstrate that progestins also induce Stat3 phosphorylation at Ser727 residue, which occurs via activation of c-Src/p42/p44 MAPK pathways in murine progestin-dependent C4HD cells and in T-47D cells. Expression of a Stat3S727A vector, which carries a serine-to-alanine substitution at codon 727, shows that Stat3Ser727 phosphorylation is required for full transcriptional activation of cyclin D1 gene expression by progestins and for in vivo Stat3 recruitment on cyclin D1 promoter. Transfection of Stat3S727A in murine and human breast cancer cells abolished progestin-induced in vitro and in vivo growth. Moreover, we found a positive correlation between progesterone receptor expression and nuclear localization of Stat3Ser727 phosphorylation in breast cancer biopsies. These data highlight Stat3 phosphorylation in Ser727 residue as a nongenomic action by progestins, necessary to promote breast cancer growth.
publishDate 2013
dc.date.none.fl_str_mv 2013-03-22
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/5548
Tkach, Mercedes; Rosemblit, Cinthia; Rivas, Martin Alfredo; Proietti Anastasi, Cecilia Jazmín; Díaz Flaqué, María Celeste; et al.; p42/p44 MAPK-mediated Stat3 Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth; Bioscientifica; Endocrine - Related Cancer; 20; 2; 22-3-2013; 197-212
1351-0088
1479-6821
url http://hdl.handle.net/11336/5548
identifier_str_mv Tkach, Mercedes; Rosemblit, Cinthia; Rivas, Martin Alfredo; Proietti Anastasi, Cecilia Jazmín; Díaz Flaqué, María Celeste; et al.; p42/p44 MAPK-mediated Stat3 Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth; Bioscientifica; Endocrine - Related Cancer; 20; 2; 22-3-2013; 197-212
1351-0088
1479-6821
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/ark/10.1530/ERC-12-0194
info:eu-repo/semantics/altIdentifier/pmid/23329648
info:eu-repo/semantics/altIdentifier/url/http://erc.endocrinology-journals.org/content/20/2/197.long
info:eu-repo/semantics/altIdentifier/doi/10.1530/ERC-12-0194
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/msword
dc.publisher.none.fl_str_mv Bioscientifica
publisher.none.fl_str_mv Bioscientifica
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.822162

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