Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer

Autores
Cerliani, Juan Pablo; Guillardoy, Tomás; Giulianelli, Sebastian Jesus; Vaque, José P.; Gutkind JS; Vanzulli, Silvia; Martins, Rubén; Zeitlin, Eduardo; Lamb, Caroline Ana; Lanari, Claudia Lee Malvina
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fibroblast growth factor (FGF) receptor 2 (FGFR-2) polymorphisms have been associated with an increase in estrogen receptor and progesterone receptor (PR)-positive breast cancer risk; however, a clear mechanistic association between FGFR-2 and steroid hormone receptors remains elusive. In previous works, we have shown a cross talk between FGF2 and progestins in mouse mammary carcinomas. To investigate the mechanisms underlying these interactions and to validate our findings in a human setting, we have used T47D human breast cancer cells and human cancer tissue samples. We showed that medroxyprogesterone acetate (MPA) and FGF2 induced cell proliferation and activation of ERK, AKT, and STAT5 in T47D and in murine C4-HI cells. Nuclear interaction between PR, FGFR-2, and STAT5 after MPA and FGF2 treatment was also showed by confocal microscopy and immunoprecipitation. This effect was associated with increased transcription of PRE and/or GAS reporter genes, and of PR/STAT5-regulated genes and proteins. Two antiprogestins and the FGFR inhibitor PD173074, specifically blocked the effects induced by FGF2 or MPA respectively. The presence of PR/FGFR-2/ STAT5 complexes bound to the PRE probe was corroborated by using NoShift transcription and chromatin immunoprecipitation of the MYC promoter. Additionally, we showed that T47D cells stably transfected with constitutively active FGFR-2 gave rise to invasive carcinomas when transplanted into NOD/SCID mice. Nuclear colocalization between PR and FGFR-2/STAT5 was also observed in human breast cancer tissues. This study represents the first demonstration of a nuclear interaction between FGFR-2 and STAT5, as PR coactivators at the DNA progesterone responsive elements, suggesting that FGFRs are valid therapeutic targets for human breast cancer treatment. ©2011 AACR.
Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Guillardoy, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Giulianelli, Sebastian Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Vaque, José P.. National Institutes of Health; Estados Unidos
Fil: Gutkind JS. National Institutes of Health; Estados Unidos
Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Martins, Rubén. Clínica Bancaria; Argentina
Fil: Zeitlin, Eduardo. Clínica Bancaria; Argentina
Fil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
Breast Cancer
Fgf2
Fibroblast Growth Factor Receptors
Mammary Carcinomas
Progesterone Receptor
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:11336/78708
Acceder
id CONICETDig_750e087ded3c42a3b26ca163738f387c
oai_identifier_str oai:ri.conicet.gov.ar:11336/78708
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancerCerliani, Juan PabloGuillardoy, TomásGiulianelli, Sebastian JesusVaque, José P.Gutkind JSVanzulli, SilviaMartins, RubénZeitlin, EduardoLamb, Caroline AnaLanari, Claudia Lee MalvinaBreast CancerFgf2Fibroblast Growth Factor ReceptorsMammary CarcinomasProgesterone Receptorhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Fibroblast growth factor (FGF) receptor 2 (FGFR-2) polymorphisms have been associated with an increase in estrogen receptor and progesterone receptor (PR)-positive breast cancer risk; however, a clear mechanistic association between FGFR-2 and steroid hormone receptors remains elusive. In previous works, we have shown a cross talk between FGF2 and progestins in mouse mammary carcinomas. To investigate the mechanisms underlying these interactions and to validate our findings in a human setting, we have used T47D human breast cancer cells and human cancer tissue samples. We showed that medroxyprogesterone acetate (MPA) and FGF2 induced cell proliferation and activation of ERK, AKT, and STAT5 in T47D and in murine C4-HI cells. Nuclear interaction between PR, FGFR-2, and STAT5 after MPA and FGF2 treatment was also showed by confocal microscopy and immunoprecipitation. This effect was associated with increased transcription of PRE and/or GAS reporter genes, and of PR/STAT5-regulated genes and proteins. Two antiprogestins and the FGFR inhibitor PD173074, specifically blocked the effects induced by FGF2 or MPA respectively. The presence of PR/FGFR-2/ STAT5 complexes bound to the PRE probe was corroborated by using NoShift transcription and chromatin immunoprecipitation of the MYC promoter. Additionally, we showed that T47D cells stably transfected with constitutively active FGFR-2 gave rise to invasive carcinomas when transplanted into NOD/SCID mice. Nuclear colocalization between PR and FGFR-2/STAT5 was also observed in human breast cancer tissues. This study represents the first demonstration of a nuclear interaction between FGFR-2 and STAT5, as PR coactivators at the DNA progesterone responsive elements, suggesting that FGFRs are valid therapeutic targets for human breast cancer treatment. ©2011 AACR.Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Guillardoy, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Giulianelli, Sebastian Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vaque, José P.. National Institutes of Health; Estados UnidosFil: Gutkind JS. National Institutes of Health; Estados UnidosFil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Martins, Rubén. Clínica Bancaria; ArgentinaFil: Zeitlin, Eduardo. Clínica Bancaria; ArgentinaFil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaAmerican Association for Cancer Research2011-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/78708Cerliani, Juan Pablo; Guillardoy, Tomás; Giulianelli, Sebastian Jesus; Vaque, José P.; Gutkind JS; et al.; Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer; American Association for Cancer Research; Cancer Research; 71; 10; 5-2011; 3720-37310008-5472CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1158/0008-5472.CAN-10-3074info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/71/10/3720info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:21:43Zoai:ri.conicet.gov.ar:11336/78708instacron: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:34982025-09-10 13:21:44.243CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer
title Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer
spellingShingle Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer
Cerliani, Juan Pablo
Breast Cancer
Fgf2
Fibroblast Growth Factor Receptors
Mammary Carcinomas
Progesterone Receptor
title_short Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer
title_full Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer
title_fullStr Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer
title_full_unstemmed Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer
title_sort Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer
dc.creator.none.fl_str_mv Cerliani, Juan Pablo
Guillardoy, Tomás
Giulianelli, Sebastian Jesus
Vaque, José P.
Gutkind JS
Vanzulli, Silvia
Martins, Rubén
Zeitlin, Eduardo
Lamb, Caroline Ana
Lanari, Claudia Lee Malvina
author Cerliani, Juan Pablo
author_facet Cerliani, Juan Pablo
Guillardoy, Tomás
Giulianelli, Sebastian Jesus
Vaque, José P.
Gutkind JS
Vanzulli, Silvia
Martins, Rubén
Zeitlin, Eduardo
Lamb, Caroline Ana
Lanari, Claudia Lee Malvina
author_role author
author2 Guillardoy, Tomás
Giulianelli, Sebastian Jesus
Vaque, José P.
Gutkind JS
Vanzulli, Silvia
Martins, Rubén
Zeitlin, Eduardo
Lamb, Caroline Ana
Lanari, Claudia Lee Malvina
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Breast Cancer
Fgf2
Fibroblast Growth Factor Receptors
Mammary Carcinomas
Progesterone Receptor
topic Breast Cancer
Fgf2
Fibroblast Growth Factor Receptors
Mammary Carcinomas
Progesterone Receptor
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Fibroblast growth factor (FGF) receptor 2 (FGFR-2) polymorphisms have been associated with an increase in estrogen receptor and progesterone receptor (PR)-positive breast cancer risk; however, a clear mechanistic association between FGFR-2 and steroid hormone receptors remains elusive. In previous works, we have shown a cross talk between FGF2 and progestins in mouse mammary carcinomas. To investigate the mechanisms underlying these interactions and to validate our findings in a human setting, we have used T47D human breast cancer cells and human cancer tissue samples. We showed that medroxyprogesterone acetate (MPA) and FGF2 induced cell proliferation and activation of ERK, AKT, and STAT5 in T47D and in murine C4-HI cells. Nuclear interaction between PR, FGFR-2, and STAT5 after MPA and FGF2 treatment was also showed by confocal microscopy and immunoprecipitation. This effect was associated with increased transcription of PRE and/or GAS reporter genes, and of PR/STAT5-regulated genes and proteins. Two antiprogestins and the FGFR inhibitor PD173074, specifically blocked the effects induced by FGF2 or MPA respectively. The presence of PR/FGFR-2/ STAT5 complexes bound to the PRE probe was corroborated by using NoShift transcription and chromatin immunoprecipitation of the MYC promoter. Additionally, we showed that T47D cells stably transfected with constitutively active FGFR-2 gave rise to invasive carcinomas when transplanted into NOD/SCID mice. Nuclear colocalization between PR and FGFR-2/STAT5 was also observed in human breast cancer tissues. This study represents the first demonstration of a nuclear interaction between FGFR-2 and STAT5, as PR coactivators at the DNA progesterone responsive elements, suggesting that FGFRs are valid therapeutic targets for human breast cancer treatment. ©2011 AACR.
Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Guillardoy, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Giulianelli, Sebastian Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Vaque, José P.. National Institutes of Health; Estados Unidos
Fil: Gutkind JS. National Institutes of Health; Estados Unidos
Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Martins, Rubén. Clínica Bancaria; Argentina
Fil: Zeitlin, Eduardo. Clínica Bancaria; Argentina
Fil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description Fibroblast growth factor (FGF) receptor 2 (FGFR-2) polymorphisms have been associated with an increase in estrogen receptor and progesterone receptor (PR)-positive breast cancer risk; however, a clear mechanistic association between FGFR-2 and steroid hormone receptors remains elusive. In previous works, we have shown a cross talk between FGF2 and progestins in mouse mammary carcinomas. To investigate the mechanisms underlying these interactions and to validate our findings in a human setting, we have used T47D human breast cancer cells and human cancer tissue samples. We showed that medroxyprogesterone acetate (MPA) and FGF2 induced cell proliferation and activation of ERK, AKT, and STAT5 in T47D and in murine C4-HI cells. Nuclear interaction between PR, FGFR-2, and STAT5 after MPA and FGF2 treatment was also showed by confocal microscopy and immunoprecipitation. This effect was associated with increased transcription of PRE and/or GAS reporter genes, and of PR/STAT5-regulated genes and proteins. Two antiprogestins and the FGFR inhibitor PD173074, specifically blocked the effects induced by FGF2 or MPA respectively. The presence of PR/FGFR-2/ STAT5 complexes bound to the PRE probe was corroborated by using NoShift transcription and chromatin immunoprecipitation of the MYC promoter. Additionally, we showed that T47D cells stably transfected with constitutively active FGFR-2 gave rise to invasive carcinomas when transplanted into NOD/SCID mice. Nuclear colocalization between PR and FGFR-2/STAT5 was also observed in human breast cancer tissues. This study represents the first demonstration of a nuclear interaction between FGFR-2 and STAT5, as PR coactivators at the DNA progesterone responsive elements, suggesting that FGFRs are valid therapeutic targets for human breast cancer treatment. ©2011 AACR.
publishDate 2011
dc.date.none.fl_str_mv 2011-05
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/11336/78708
Cerliani, Juan Pablo; Guillardoy, Tomás; Giulianelli, Sebastian Jesus; Vaque, José P.; Gutkind JS; et al.; Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer; American Association for Cancer Research; Cancer Research; 71; 10; 5-2011; 3720-3731
0008-5472
CONICET Digital
CONICET
url http://hdl.handle.net/11336/78708
identifier_str_mv Cerliani, Juan Pablo; Guillardoy, Tomás; Giulianelli, Sebastian Jesus; Vaque, José P.; Gutkind JS; et al.; Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer; American Association for Cancer Research; Cancer Research; 71; 10; 5-2011; 3720-3731
0008-5472
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1158/0008-5472.CAN-10-3074
info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/71/10/3720
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/pdf
application/pdf
dc.publisher.none.fl_str_mv American Association for Cancer Research
publisher.none.fl_str_mv American Association for Cancer Research
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 12.48226

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