Heregulin co-opts PR transcriptional action via stat3 role as a coregulator to drive cancer growth

Autores
Proietti Anastasi, Cecilia Jazmín; Izzo, Franco; Díaz Flaqué, María Celeste; Cordo Russo, Rosalia Ines; Venturutti, Leandro; de Martino, Mara; Pineda, Viviana; Muñoz, Sergio; Guzman, Pablo; Roa, Juan Carlos; Schillaci, Roxana; Elizalde, Patricia Virginia
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Accumulated findings have demonstrated the presence of bidirectional interactions between progesterone receptor (PR) and the ErbB family of receptor tyrosine kinases signaling pathways in breast cancer. We previously revealed signal transducer and activator of transcription 3 (Stat3) as a nodal convergence point between said signaling pathways proving that Stat3 is activated by one of the ErbBs’ ligands, heregulin (HRG)β1 via ErbB2 and through the co-option of PR as a signaling molecule. Here, we found that HRGβ1 induced Stat3 recruitment to the promoters of the progestin-regulated cell cycle modulators Bcl-XLand p21CIP1and also stimulated Stat3 binding to the mouse mammary tumor virus promoter, which carries consensus progesterone response elements. Interestingly, HRGβ1-activated Stat3 displayed differential functions on PR activity depending on the promoter bound. Indeed, Stat3 was required for PR binding in bcl-X, p21CIP1, and c-myc promoters while exerting a PR coactivator function on the mouse mammary tumor virus promoter. Stat3 also proved to be necessary for HRGβ1-induced in vivo tumor growth. Our results endow Stat3 a novel function as a coregulator of HRGβ1-activated PR to promote breast cancer growth. These findings underscore the importance of understanding the complex interactions between PR and other regulatory factors, such as Stat3, that contribute to determine the contextdependent transcriptional actions of PR.
Fil: Proietti Anastasi, Cecilia Jazmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Izzo, Franco. 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: Cordo Russo, Rosalia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Venturutti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: de Martino, Mara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Pineda, Viviana. Universidad de la Frontera. Departamento de Anatomía Patológica; Chile
Fil: Muñoz, Sergio. Universidad de la Frontera. Departamento de Anatomía Patológica; Chile
Fil: Guzman, Pablo. Universidad de la Frontera. Departamento de Anatomía Patológica; Chile
Fil: Roa, Juan Carlos. Universidad de la Frontera. Departamento de Anatomía Patológica; Chile. Pontificia Universidad Católica de Chile. Departamento de Anatomía Patológica; Chile. Pontificia Universidad Católica de Chile. Advanced Center for Chronic Diseases; Chile
Fil: Schillaci, Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Elizalde, Patricia Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Materia
Progesterone Receptor
Stat3
Breast Cancer
Heregulin
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:11336/3266
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/3266
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Heregulin co-opts PR transcriptional action via stat3 role as a coregulator to drive cancer growthProietti Anastasi, Cecilia JazmínIzzo, FrancoDíaz Flaqué, María CelesteCordo Russo, Rosalia InesVenturutti, Leandrode Martino, MaraPineda, VivianaMuñoz, SergioGuzman, PabloRoa, Juan CarlosSchillaci, RoxanaElizalde, Patricia VirginiaProgesterone ReceptorStat3Breast CancerHeregulinhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Accumulated findings have demonstrated the presence of bidirectional interactions between progesterone receptor (PR) and the ErbB family of receptor tyrosine kinases signaling pathways in breast cancer. We previously revealed signal transducer and activator of transcription 3 (Stat3) as a nodal convergence point between said signaling pathways proving that Stat3 is activated by one of the ErbBs’ ligands, heregulin (HRG)β1 via ErbB2 and through the co-option of PR as a signaling molecule. Here, we found that HRGβ1 induced Stat3 recruitment to the promoters of the progestin-regulated cell cycle modulators Bcl-XLand p21CIP1and also stimulated Stat3 binding to the mouse mammary tumor virus promoter, which carries consensus progesterone response elements. Interestingly, HRGβ1-activated Stat3 displayed differential functions on PR activity depending on the promoter bound. Indeed, Stat3 was required for PR binding in bcl-X, p21CIP1, and c-myc promoters while exerting a PR coactivator function on the mouse mammary tumor virus promoter. Stat3 also proved to be necessary for HRGβ1-induced in vivo tumor growth. Our results endow Stat3 a novel function as a coregulator of HRGβ1-activated PR to promote breast cancer growth. These findings underscore the importance of understanding the complex interactions between PR and other regulatory factors, such as Stat3, that contribute to determine the contextdependent transcriptional actions of PR.Fil: Proietti Anastasi, Cecilia Jazmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Izzo, Franco. 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: Cordo Russo, Rosalia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Venturutti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: de Martino, Mara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Pineda, Viviana. Universidad de la Frontera. Departamento de Anatomía Patológica; ChileFil: Muñoz, Sergio. Universidad de la Frontera. Departamento de Anatomía Patológica; ChileFil: Guzman, Pablo. Universidad de la Frontera. Departamento de Anatomía Patológica; ChileFil: Roa, Juan Carlos. Universidad de la Frontera. Departamento de Anatomía Patológica; Chile. Pontificia Universidad Católica de Chile. Departamento de Anatomía Patológica; Chile. Pontificia Universidad Católica de Chile. Advanced Center for Chronic Diseases; ChileFil: Schillaci, Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Elizalde, Patricia Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaEndocrine Society2015-09-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/3266Proietti Anastasi, Cecilia Jazmín; Izzo, Franco; Díaz Flaqué, María Celeste; Cordo Russo, Rosalia Ines; Venturutti, Leandro; et al.; Heregulin co-opts PR transcriptional action via stat3 role as a coregulator to drive cancer growth; Endocrine Society; Molecular Endocrinology; 29; 10; 4-9-2015; 1468-14850888-88091944-9917enginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/mend/article/29/10/1468/2556425info:eu-repo/semantics/altIdentifier/doi/10.1210/me.2015-1170info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:58:27Zoai:ri.conicet.gov.ar:11336/3266instacron: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:34982025-09-29 09:58:27.803CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Heregulin co-opts PR transcriptional action via stat3 role as a coregulator to drive cancer growth
title Heregulin co-opts PR transcriptional action via stat3 role as a coregulator to drive cancer growth
spellingShingle Heregulin co-opts PR transcriptional action via stat3 role as a coregulator to drive cancer growth
Proietti Anastasi, Cecilia Jazmín
Progesterone Receptor
Stat3
Breast Cancer
Heregulin
title_short Heregulin co-opts PR transcriptional action via stat3 role as a coregulator to drive cancer growth
title_full Heregulin co-opts PR transcriptional action via stat3 role as a coregulator to drive cancer growth
title_fullStr Heregulin co-opts PR transcriptional action via stat3 role as a coregulator to drive cancer growth
title_full_unstemmed Heregulin co-opts PR transcriptional action via stat3 role as a coregulator to drive cancer growth
title_sort Heregulin co-opts PR transcriptional action via stat3 role as a coregulator to drive cancer growth
dc.creator.none.fl_str_mv Proietti Anastasi, Cecilia Jazmín
Izzo, Franco
Díaz Flaqué, María Celeste
Cordo Russo, Rosalia Ines
Venturutti, Leandro
de Martino, Mara
Pineda, Viviana
Muñoz, Sergio
Guzman, Pablo
Roa, Juan Carlos
Schillaci, Roxana
Elizalde, Patricia Virginia
author Proietti Anastasi, Cecilia Jazmín
author_facet Proietti Anastasi, Cecilia Jazmín
Izzo, Franco
Díaz Flaqué, María Celeste
Cordo Russo, Rosalia Ines
Venturutti, Leandro
de Martino, Mara
Pineda, Viviana
Muñoz, Sergio
Guzman, Pablo
Roa, Juan Carlos
Schillaci, Roxana
Elizalde, Patricia Virginia
author_role author
author2 Izzo, Franco
Díaz Flaqué, María Celeste
Cordo Russo, Rosalia Ines
Venturutti, Leandro
de Martino, Mara
Pineda, Viviana
Muñoz, Sergio
Guzman, Pablo
Roa, Juan Carlos
Schillaci, Roxana
Elizalde, Patricia Virginia
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Progesterone Receptor
Stat3
Breast Cancer
Heregulin
topic Progesterone Receptor
Stat3
Breast Cancer
Heregulin
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Accumulated findings have demonstrated the presence of bidirectional interactions between progesterone receptor (PR) and the ErbB family of receptor tyrosine kinases signaling pathways in breast cancer. We previously revealed signal transducer and activator of transcription 3 (Stat3) as a nodal convergence point between said signaling pathways proving that Stat3 is activated by one of the ErbBs’ ligands, heregulin (HRG)β1 via ErbB2 and through the co-option of PR as a signaling molecule. Here, we found that HRGβ1 induced Stat3 recruitment to the promoters of the progestin-regulated cell cycle modulators Bcl-XLand p21CIP1and also stimulated Stat3 binding to the mouse mammary tumor virus promoter, which carries consensus progesterone response elements. Interestingly, HRGβ1-activated Stat3 displayed differential functions on PR activity depending on the promoter bound. Indeed, Stat3 was required for PR binding in bcl-X, p21CIP1, and c-myc promoters while exerting a PR coactivator function on the mouse mammary tumor virus promoter. Stat3 also proved to be necessary for HRGβ1-induced in vivo tumor growth. Our results endow Stat3 a novel function as a coregulator of HRGβ1-activated PR to promote breast cancer growth. These findings underscore the importance of understanding the complex interactions between PR and other regulatory factors, such as Stat3, that contribute to determine the contextdependent transcriptional actions of PR.
Fil: Proietti Anastasi, Cecilia Jazmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Izzo, Franco. 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: Cordo Russo, Rosalia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Venturutti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: de Martino, Mara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Pineda, Viviana. Universidad de la Frontera. Departamento de Anatomía Patológica; Chile
Fil: Muñoz, Sergio. Universidad de la Frontera. Departamento de Anatomía Patológica; Chile
Fil: Guzman, Pablo. Universidad de la Frontera. Departamento de Anatomía Patológica; Chile
Fil: Roa, Juan Carlos. Universidad de la Frontera. Departamento de Anatomía Patológica; Chile. Pontificia Universidad Católica de Chile. Departamento de Anatomía Patológica; Chile. Pontificia Universidad Católica de Chile. Advanced Center for Chronic Diseases; Chile
Fil: Schillaci, Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Elizalde, Patricia Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
description Accumulated findings have demonstrated the presence of bidirectional interactions between progesterone receptor (PR) and the ErbB family of receptor tyrosine kinases signaling pathways in breast cancer. We previously revealed signal transducer and activator of transcription 3 (Stat3) as a nodal convergence point between said signaling pathways proving that Stat3 is activated by one of the ErbBs’ ligands, heregulin (HRG)β1 via ErbB2 and through the co-option of PR as a signaling molecule. Here, we found that HRGβ1 induced Stat3 recruitment to the promoters of the progestin-regulated cell cycle modulators Bcl-XLand p21CIP1and also stimulated Stat3 binding to the mouse mammary tumor virus promoter, which carries consensus progesterone response elements. Interestingly, HRGβ1-activated Stat3 displayed differential functions on PR activity depending on the promoter bound. Indeed, Stat3 was required for PR binding in bcl-X, p21CIP1, and c-myc promoters while exerting a PR coactivator function on the mouse mammary tumor virus promoter. Stat3 also proved to be necessary for HRGβ1-induced in vivo tumor growth. Our results endow Stat3 a novel function as a coregulator of HRGβ1-activated PR to promote breast cancer growth. These findings underscore the importance of understanding the complex interactions between PR and other regulatory factors, such as Stat3, that contribute to determine the contextdependent transcriptional actions of PR.
publishDate 2015
dc.date.none.fl_str_mv 2015-09-04
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/11336/3266
Proietti Anastasi, Cecilia Jazmín; Izzo, Franco; Díaz Flaqué, María Celeste; Cordo Russo, Rosalia Ines; Venturutti, Leandro; et al.; Heregulin co-opts PR transcriptional action via stat3 role as a coregulator to drive cancer growth; Endocrine Society; Molecular Endocrinology; 29; 10; 4-9-2015; 1468-1485
0888-8809
1944-9917
url http://hdl.handle.net/11336/3266
identifier_str_mv Proietti Anastasi, Cecilia Jazmín; Izzo, Franco; Díaz Flaqué, María Celeste; Cordo Russo, Rosalia Ines; Venturutti, Leandro; et al.; Heregulin co-opts PR transcriptional action via stat3 role as a coregulator to drive cancer growth; Endocrine Society; Molecular Endocrinology; 29; 10; 4-9-2015; 1468-1485
0888-8809
1944-9917
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/mend/article/29/10/1468/2556425
info:eu-repo/semantics/altIdentifier/doi/10.1210/me.2015-1170
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
dc.publisher.none.fl_str_mv Endocrine Society
publisher.none.fl_str_mv Endocrine Society
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 13.070432

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