Alterations in c-Src/HER1 and Estrogen Receptor alpha signaling pathways in mammary gland and tumors of Hexachlorobenzene-treated rats

Autores
Peña, Delfina; Pontillo, Carolina Andrea; García, María Alejandra; Cocca, Claudia Marcela; Alvarez, Laura; Chiappini, Florencia Ana; Bourguignon, Nadia; Frahm, Isabel Leonor; Bergoc, Rosa Maria; Kleiman de Pisarev, Diana; Randi, Andrea Silvana
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hexachlorobenzene (HCB) is an organochlorine pesticide that acts as an endocrine disruptor in humans and rodents. The development of breast cancer strongly depends on endocrine conditions modulated by environmental factors. We have demonstrated that HCB is a tumor co carcinogen in rats and an inducer of proliferation in MCF-7 cells, in an estrogen receptor (ER)-dependent manner, and of migration in MDA-MB-231 breast cancer cell line. In the present study, we examined HCB effect on c-Src/human epidermal growth factor receptor (HER1) and ER signaling pathways in mammary glands and in N-nitroso-N-methylurea (NMU)-induced mammary tumors in rats. Furthermore, we evaluated histopathological changes and serum hormone levels. Rats were separated into four groups: control, HCB (100 mg/kg b.w.), NMU (50 mg/kg b.w.) and NMU-HCB. Our data show that HCB increases c-Src and HER1 activation, c-Src/HER1 association, and Y699-STAT5b and ERK1/2 phosphorylation in mammary glands. HCB also enhances Y537-ER phosphorylation and ER/c-Src physical interaction. In tumors, HCB also induces c-Src and HER1 activation, c-Src/HER1 association, as well as T308-Akt and Y699-STAT5b phosphorylation. In addition, the pesticide increases ER protein content and decreases p-Y537-ER levels and ER/c-Src association in tumors. HCB increases serum 17-beta estradiol and prolactin contents and decreases progesterone, FSH and LH levels in rats without tumors, while the opposite effect was observed in rats with tumors. Taken together, our results indicate that HCB induces an estrogenic effect in mammary gland, increasing c-Src/HER1 and ER signaling pathways. HCB stimulates cSrc/HER1 pathway, but decreases ER activity in tumors, appearing to shift them towards a higher malignancy phenotype.
Fil: Peña, Delfina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Pontillo, Carolina Andrea. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: García, María Alejandra. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Cocca, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Alvarez, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Chiappini, Florencia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Bourguignon, Nadia. 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: Frahm, Isabel Leonor. Sanatorio Mater Dei;
Fil: Bergoc, Rosa Maria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Kleiman de Pisarev, Diana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Randi, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Materia
HEXACHLOROBENZENE
MAMMARY GLAND
TUMOR PROMOTION
ESTROGEN RECEPTOR
HER1
C-SRC
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:11336/270934
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/270934
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Alterations in c-Src/HER1 and Estrogen Receptor alpha signaling pathways in mammary gland and tumors of Hexachlorobenzene-treated ratsPeña, DelfinaPontillo, Carolina AndreaGarcía, María AlejandraCocca, Claudia MarcelaAlvarez, LauraChiappini, Florencia AnaBourguignon, NadiaFrahm, Isabel LeonorBergoc, Rosa MariaKleiman de Pisarev, DianaRandi, Andrea SilvanaHEXACHLOROBENZENEMAMMARY GLANDTUMOR PROMOTIONESTROGEN RECEPTORHER1C-SRChttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Hexachlorobenzene (HCB) is an organochlorine pesticide that acts as an endocrine disruptor in humans and rodents. The development of breast cancer strongly depends on endocrine conditions modulated by environmental factors. We have demonstrated that HCB is a tumor co carcinogen in rats and an inducer of proliferation in MCF-7 cells, in an estrogen receptor (ER)-dependent manner, and of migration in MDA-MB-231 breast cancer cell line. In the present study, we examined HCB effect on c-Src/human epidermal growth factor receptor (HER1) and ER signaling pathways in mammary glands and in N-nitroso-N-methylurea (NMU)-induced mammary tumors in rats. Furthermore, we evaluated histopathological changes and serum hormone levels. Rats were separated into four groups: control, HCB (100 mg/kg b.w.), NMU (50 mg/kg b.w.) and NMU-HCB. Our data show that HCB increases c-Src and HER1 activation, c-Src/HER1 association, and Y699-STAT5b and ERK1/2 phosphorylation in mammary glands. HCB also enhances Y537-ER phosphorylation and ER/c-Src physical interaction. In tumors, HCB also induces c-Src and HER1 activation, c-Src/HER1 association, as well as T308-Akt and Y699-STAT5b phosphorylation. In addition, the pesticide increases ER protein content and decreases p-Y537-ER levels and ER/c-Src association in tumors. HCB increases serum 17-beta estradiol and prolactin contents and decreases progesterone, FSH and LH levels in rats without tumors, while the opposite effect was observed in rats with tumors. Taken together, our results indicate that HCB induces an estrogenic effect in mammary gland, increasing c-Src/HER1 and ER signaling pathways. HCB stimulates cSrc/HER1 pathway, but decreases ER activity in tumors, appearing to shift them towards a higher malignancy phenotype.Fil: Peña, Delfina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Pontillo, Carolina Andrea. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: García, María Alejandra. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Cocca, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Alvarez, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Chiappini, Florencia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Bourguignon, Nadia. 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: Frahm, Isabel Leonor. Sanatorio Mater Dei;Fil: Bergoc, Rosa Maria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Kleiman de Pisarev, Diana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Randi, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaElsevier Ireland2012-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/270934Peña, Delfina; Pontillo, Carolina Andrea; García, María Alejandra; Cocca, Claudia Marcela; Alvarez, Laura; et al.; Alterations in c-Src/HER1 and Estrogen Receptor alpha signaling pathways in mammary gland and tumors of Hexachlorobenzene-treated rats; Elsevier Ireland; Toxicology; 12-2012; 68-770300-483XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0300483X11005476info:eu-repo/semantics/altIdentifier/doi/10.1016/j.tox.2011.12.012info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:40:38Zoai:ri.conicet.gov.ar:11336/270934instacron: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 09:40:39.253CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Alterations in c-Src/HER1 and Estrogen Receptor alpha signaling pathways in mammary gland and tumors of Hexachlorobenzene-treated rats
title Alterations in c-Src/HER1 and Estrogen Receptor alpha signaling pathways in mammary gland and tumors of Hexachlorobenzene-treated rats
spellingShingle Alterations in c-Src/HER1 and Estrogen Receptor alpha signaling pathways in mammary gland and tumors of Hexachlorobenzene-treated rats
Peña, Delfina
HEXACHLOROBENZENE
MAMMARY GLAND
TUMOR PROMOTION
ESTROGEN RECEPTOR
HER1
C-SRC
title_short Alterations in c-Src/HER1 and Estrogen Receptor alpha signaling pathways in mammary gland and tumors of Hexachlorobenzene-treated rats
title_full Alterations in c-Src/HER1 and Estrogen Receptor alpha signaling pathways in mammary gland and tumors of Hexachlorobenzene-treated rats
title_fullStr Alterations in c-Src/HER1 and Estrogen Receptor alpha signaling pathways in mammary gland and tumors of Hexachlorobenzene-treated rats
title_full_unstemmed Alterations in c-Src/HER1 and Estrogen Receptor alpha signaling pathways in mammary gland and tumors of Hexachlorobenzene-treated rats
title_sort Alterations in c-Src/HER1 and Estrogen Receptor alpha signaling pathways in mammary gland and tumors of Hexachlorobenzene-treated rats
dc.creator.none.fl_str_mv Peña, Delfina
Pontillo, Carolina Andrea
García, María Alejandra
Cocca, Claudia Marcela
Alvarez, Laura
Chiappini, Florencia Ana
Bourguignon, Nadia
Frahm, Isabel Leonor
Bergoc, Rosa Maria
Kleiman de Pisarev, Diana
Randi, Andrea Silvana
author Peña, Delfina
author_facet Peña, Delfina
Pontillo, Carolina Andrea
García, María Alejandra
Cocca, Claudia Marcela
Alvarez, Laura
Chiappini, Florencia Ana
Bourguignon, Nadia
Frahm, Isabel Leonor
Bergoc, Rosa Maria
Kleiman de Pisarev, Diana
Randi, Andrea Silvana
author_role author
author2 Pontillo, Carolina Andrea
García, María Alejandra
Cocca, Claudia Marcela
Alvarez, Laura
Chiappini, Florencia Ana
Bourguignon, Nadia
Frahm, Isabel Leonor
Bergoc, Rosa Maria
Kleiman de Pisarev, Diana
Randi, Andrea Silvana
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HEXACHLOROBENZENE
MAMMARY GLAND
TUMOR PROMOTION
ESTROGEN RECEPTOR
HER1
C-SRC
topic HEXACHLOROBENZENE
MAMMARY GLAND
TUMOR PROMOTION
ESTROGEN RECEPTOR
HER1
C-SRC
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hexachlorobenzene (HCB) is an organochlorine pesticide that acts as an endocrine disruptor in humans and rodents. The development of breast cancer strongly depends on endocrine conditions modulated by environmental factors. We have demonstrated that HCB is a tumor co carcinogen in rats and an inducer of proliferation in MCF-7 cells, in an estrogen receptor (ER)-dependent manner, and of migration in MDA-MB-231 breast cancer cell line. In the present study, we examined HCB effect on c-Src/human epidermal growth factor receptor (HER1) and ER signaling pathways in mammary glands and in N-nitroso-N-methylurea (NMU)-induced mammary tumors in rats. Furthermore, we evaluated histopathological changes and serum hormone levels. Rats were separated into four groups: control, HCB (100 mg/kg b.w.), NMU (50 mg/kg b.w.) and NMU-HCB. Our data show that HCB increases c-Src and HER1 activation, c-Src/HER1 association, and Y699-STAT5b and ERK1/2 phosphorylation in mammary glands. HCB also enhances Y537-ER phosphorylation and ER/c-Src physical interaction. In tumors, HCB also induces c-Src and HER1 activation, c-Src/HER1 association, as well as T308-Akt and Y699-STAT5b phosphorylation. In addition, the pesticide increases ER protein content and decreases p-Y537-ER levels and ER/c-Src association in tumors. HCB increases serum 17-beta estradiol and prolactin contents and decreases progesterone, FSH and LH levels in rats without tumors, while the opposite effect was observed in rats with tumors. Taken together, our results indicate that HCB induces an estrogenic effect in mammary gland, increasing c-Src/HER1 and ER signaling pathways. HCB stimulates cSrc/HER1 pathway, but decreases ER activity in tumors, appearing to shift them towards a higher malignancy phenotype.
Fil: Peña, Delfina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Pontillo, Carolina Andrea. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: García, María Alejandra. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Cocca, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Alvarez, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Chiappini, Florencia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Bourguignon, Nadia. 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: Frahm, Isabel Leonor. Sanatorio Mater Dei;
Fil: Bergoc, Rosa Maria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Kleiman de Pisarev, Diana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Randi, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
description Hexachlorobenzene (HCB) is an organochlorine pesticide that acts as an endocrine disruptor in humans and rodents. The development of breast cancer strongly depends on endocrine conditions modulated by environmental factors. We have demonstrated that HCB is a tumor co carcinogen in rats and an inducer of proliferation in MCF-7 cells, in an estrogen receptor (ER)-dependent manner, and of migration in MDA-MB-231 breast cancer cell line. In the present study, we examined HCB effect on c-Src/human epidermal growth factor receptor (HER1) and ER signaling pathways in mammary glands and in N-nitroso-N-methylurea (NMU)-induced mammary tumors in rats. Furthermore, we evaluated histopathological changes and serum hormone levels. Rats were separated into four groups: control, HCB (100 mg/kg b.w.), NMU (50 mg/kg b.w.) and NMU-HCB. Our data show that HCB increases c-Src and HER1 activation, c-Src/HER1 association, and Y699-STAT5b and ERK1/2 phosphorylation in mammary glands. HCB also enhances Y537-ER phosphorylation and ER/c-Src physical interaction. In tumors, HCB also induces c-Src and HER1 activation, c-Src/HER1 association, as well as T308-Akt and Y699-STAT5b phosphorylation. In addition, the pesticide increases ER protein content and decreases p-Y537-ER levels and ER/c-Src association in tumors. HCB increases serum 17-beta estradiol and prolactin contents and decreases progesterone, FSH and LH levels in rats without tumors, while the opposite effect was observed in rats with tumors. Taken together, our results indicate that HCB induces an estrogenic effect in mammary gland, increasing c-Src/HER1 and ER signaling pathways. HCB stimulates cSrc/HER1 pathway, but decreases ER activity in tumors, appearing to shift them towards a higher malignancy phenotype.
publishDate 2012
dc.date.none.fl_str_mv 2012-12
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/11336/270934
Peña, Delfina; Pontillo, Carolina Andrea; García, María Alejandra; Cocca, Claudia Marcela; Alvarez, Laura; et al.; Alterations in c-Src/HER1 and Estrogen Receptor alpha signaling pathways in mammary gland and tumors of Hexachlorobenzene-treated rats; Elsevier Ireland; Toxicology; 12-2012; 68-77
0300-483X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/270934
identifier_str_mv Peña, Delfina; Pontillo, Carolina Andrea; García, María Alejandra; Cocca, Claudia Marcela; Alvarez, Laura; et al.; Alterations in c-Src/HER1 and Estrogen Receptor alpha signaling pathways in mammary gland and tumors of Hexachlorobenzene-treated rats; Elsevier Ireland; Toxicology; 12-2012; 68-77
0300-483X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0300483X11005476
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.tox.2011.12.012
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/
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application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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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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