Activation of c-Src/HER1/STAT5b and HER1/ERK1/2 Signaling Pathways and Cell Migration by Hexachlorobenzene in MDA-MB-231 Human Breast Cancer Cell Line

Autores
Pontillo, Carolina Andrea; García, María A.; Peña, Delfina; Cocca, Claudia Marcela; Chiappini, Florencia Ana; Alvarez, Laura; Kleiman, Diana Leonor; Randi, Andrea Silvana
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hexachlorobenzene (HCB) is a widespread environmental pollutant. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR) protein. HCB is a tumor cocarcinogen in rat mammary gland and an inducer of cell proliferation and c-Src kinase activity in MCF-7 breast cancer cells. This study was carried out to investigate HCB action on c-Src and the human epidermal growth factor receptor (HER1) activities and their downstream signaling pathways, Akt, extracellular-signal-regulated kinase (ERK1/2), and signal transducers and activators of transcription (STAT) 5b, as well as on cell migration in a human breast cancer cell line, MDA-MB-231. We also investigated whether the AhR is involved in HCB-induced effects. We have demonstrated that HCB (0.05μM) produces an early increase of Y416-c-Src, Y845-HER1, Y699-STAT5b, and ERK1/2 phosphorylation. Moreover, our results have shown that the pesticide (15 min) activates these pathways in a dose-dependent manner (0.005, 0.05, 0.5, and 5μM). In contrast, HCB does not alter T308-Akt activation. Pretreatment with a specific inhibitor for c-Src (4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d]pyrimidine [PP2]) prevents Y845-HER1 and Y699-STAT5b phosphorylation. AG1478, a specific HER1 inhibitor, abrogates HCB-induced STAT5b and ERK1/2 activation, whereas 4,7-orthophenanthroline and α-naphthoflavone, two AhR antagonists, prevent HCB-induced STAT5b and ERK1/2 phosphorylation. HCB enhances cell migration evaluated by scratch motility and transwell assays. Pretreatment with PP2, AG1478, and 4,7-orthophenanthroline suppresses HCB-induced cell migration. These results demonstrate that HCB stimulates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways in MDA-MB-231. c-Src, HER1, and AhR are involved in HCB-induced increase in cell migration. The present study makes a significant contribution to the molecular mechanism of action of HCB in mammary carcinogenesis.
Fil: Pontillo, Carolina Andrea. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: García, María A.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina
Fil: Peña, Delfina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Cocca, Claudia Marcela. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Chiappini, Florencia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; 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; Argentina
Fil: Kleiman, Diana Leonor. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Randi, Andrea Silvana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Materia
Hexaclorobenceno
AhR
MDA-MB-231
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:11336/113525
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Activation of c-Src/HER1/STAT5b and HER1/ERK1/2 Signaling Pathways and Cell Migration by Hexachlorobenzene in MDA-MB-231 Human Breast Cancer Cell LinePontillo, Carolina AndreaGarcía, María A.Peña, DelfinaCocca, Claudia MarcelaChiappini, Florencia AnaAlvarez, LauraKleiman, Diana LeonorRandi, Andrea SilvanaHexaclorobencenoAhRMDA-MB-231c-Srchttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Hexachlorobenzene (HCB) is a widespread environmental pollutant. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR) protein. HCB is a tumor cocarcinogen in rat mammary gland and an inducer of cell proliferation and c-Src kinase activity in MCF-7 breast cancer cells. This study was carried out to investigate HCB action on c-Src and the human epidermal growth factor receptor (HER1) activities and their downstream signaling pathways, Akt, extracellular-signal-regulated kinase (ERK1/2), and signal transducers and activators of transcription (STAT) 5b, as well as on cell migration in a human breast cancer cell line, MDA-MB-231. We also investigated whether the AhR is involved in HCB-induced effects. We have demonstrated that HCB (0.05μM) produces an early increase of Y416-c-Src, Y845-HER1, Y699-STAT5b, and ERK1/2 phosphorylation. Moreover, our results have shown that the pesticide (15 min) activates these pathways in a dose-dependent manner (0.005, 0.05, 0.5, and 5μM). In contrast, HCB does not alter T308-Akt activation. Pretreatment with a specific inhibitor for c-Src (4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d]pyrimidine [PP2]) prevents Y845-HER1 and Y699-STAT5b phosphorylation. AG1478, a specific HER1 inhibitor, abrogates HCB-induced STAT5b and ERK1/2 activation, whereas 4,7-orthophenanthroline and α-naphthoflavone, two AhR antagonists, prevent HCB-induced STAT5b and ERK1/2 phosphorylation. HCB enhances cell migration evaluated by scratch motility and transwell assays. Pretreatment with PP2, AG1478, and 4,7-orthophenanthroline suppresses HCB-induced cell migration. These results demonstrate that HCB stimulates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways in MDA-MB-231. c-Src, HER1, and AhR are involved in HCB-induced increase in cell migration. The present study makes a significant contribution to the molecular mechanism of action of HCB in mammary carcinogenesis.Fil: Pontillo, Carolina Andrea. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: García, María A.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; ArgentinaFil: Peña, Delfina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Cocca, Claudia Marcela. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Chiappini, Florencia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; 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; ArgentinaFil: Kleiman, Diana Leonor. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Randi, Andrea Silvana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaOxford University Press2011-04info: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/pdfhttp://hdl.handle.net/11336/113525Pontillo, Carolina Andrea; García, María A.; Peña, Delfina; Cocca, Claudia Marcela; Chiappini, Florencia Ana; et al.; Activation of c-Src/HER1/STAT5b and HER1/ERK1/2 Signaling Pathways and Cell Migration by Hexachlorobenzene in MDA-MB-231 Human Breast Cancer Cell Line; Oxford University Press; Toxicological Sciences; 120; 2; 4-2011; 284-2961096-6080CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kfq390info:eu-repo/semantics/altIdentifier/doi/10.1093/toxsci/kfq390info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-29T11:49:23Zoai:ri.conicet.gov.ar:11336/113525instacron: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:34982025-10-29 11:49:23.432CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Activation of c-Src/HER1/STAT5b and HER1/ERK1/2 Signaling Pathways and Cell Migration by Hexachlorobenzene in MDA-MB-231 Human Breast Cancer Cell Line
title Activation of c-Src/HER1/STAT5b and HER1/ERK1/2 Signaling Pathways and Cell Migration by Hexachlorobenzene in MDA-MB-231 Human Breast Cancer Cell Line
spellingShingle Activation of c-Src/HER1/STAT5b and HER1/ERK1/2 Signaling Pathways and Cell Migration by Hexachlorobenzene in MDA-MB-231 Human Breast Cancer Cell Line
Pontillo, Carolina Andrea
Hexaclorobenceno
AhR
MDA-MB-231
c-Src
title_short Activation of c-Src/HER1/STAT5b and HER1/ERK1/2 Signaling Pathways and Cell Migration by Hexachlorobenzene in MDA-MB-231 Human Breast Cancer Cell Line
title_full Activation of c-Src/HER1/STAT5b and HER1/ERK1/2 Signaling Pathways and Cell Migration by Hexachlorobenzene in MDA-MB-231 Human Breast Cancer Cell Line
title_fullStr Activation of c-Src/HER1/STAT5b and HER1/ERK1/2 Signaling Pathways and Cell Migration by Hexachlorobenzene in MDA-MB-231 Human Breast Cancer Cell Line
title_full_unstemmed Activation of c-Src/HER1/STAT5b and HER1/ERK1/2 Signaling Pathways and Cell Migration by Hexachlorobenzene in MDA-MB-231 Human Breast Cancer Cell Line
title_sort Activation of c-Src/HER1/STAT5b and HER1/ERK1/2 Signaling Pathways and Cell Migration by Hexachlorobenzene in MDA-MB-231 Human Breast Cancer Cell Line
dc.creator.none.fl_str_mv Pontillo, Carolina Andrea
García, María A.
Peña, Delfina
Cocca, Claudia Marcela
Chiappini, Florencia Ana
Alvarez, Laura
Kleiman, Diana Leonor
Randi, Andrea Silvana
author Pontillo, Carolina Andrea
author_facet Pontillo, Carolina Andrea
García, María A.
Peña, Delfina
Cocca, Claudia Marcela
Chiappini, Florencia Ana
Alvarez, Laura
Kleiman, Diana Leonor
Randi, Andrea Silvana
author_role author
author2 García, María A.
Peña, Delfina
Cocca, Claudia Marcela
Chiappini, Florencia Ana
Alvarez, Laura
Kleiman, Diana Leonor
Randi, Andrea Silvana
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hexaclorobenceno
AhR
MDA-MB-231
c-Src
topic Hexaclorobenceno
AhR
MDA-MB-231
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 a widespread environmental pollutant. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR) protein. HCB is a tumor cocarcinogen in rat mammary gland and an inducer of cell proliferation and c-Src kinase activity in MCF-7 breast cancer cells. This study was carried out to investigate HCB action on c-Src and the human epidermal growth factor receptor (HER1) activities and their downstream signaling pathways, Akt, extracellular-signal-regulated kinase (ERK1/2), and signal transducers and activators of transcription (STAT) 5b, as well as on cell migration in a human breast cancer cell line, MDA-MB-231. We also investigated whether the AhR is involved in HCB-induced effects. We have demonstrated that HCB (0.05μM) produces an early increase of Y416-c-Src, Y845-HER1, Y699-STAT5b, and ERK1/2 phosphorylation. Moreover, our results have shown that the pesticide (15 min) activates these pathways in a dose-dependent manner (0.005, 0.05, 0.5, and 5μM). In contrast, HCB does not alter T308-Akt activation. Pretreatment with a specific inhibitor for c-Src (4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d]pyrimidine [PP2]) prevents Y845-HER1 and Y699-STAT5b phosphorylation. AG1478, a specific HER1 inhibitor, abrogates HCB-induced STAT5b and ERK1/2 activation, whereas 4,7-orthophenanthroline and α-naphthoflavone, two AhR antagonists, prevent HCB-induced STAT5b and ERK1/2 phosphorylation. HCB enhances cell migration evaluated by scratch motility and transwell assays. Pretreatment with PP2, AG1478, and 4,7-orthophenanthroline suppresses HCB-induced cell migration. These results demonstrate that HCB stimulates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways in MDA-MB-231. c-Src, HER1, and AhR are involved in HCB-induced increase in cell migration. The present study makes a significant contribution to the molecular mechanism of action of HCB in mammary carcinogenesis.
Fil: Pontillo, Carolina Andrea. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: García, María A.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina
Fil: Peña, Delfina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Cocca, Claudia Marcela. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Chiappini, Florencia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; 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; Argentina
Fil: Kleiman, Diana Leonor. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Randi, Andrea Silvana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
description Hexachlorobenzene (HCB) is a widespread environmental pollutant. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR) protein. HCB is a tumor cocarcinogen in rat mammary gland and an inducer of cell proliferation and c-Src kinase activity in MCF-7 breast cancer cells. This study was carried out to investigate HCB action on c-Src and the human epidermal growth factor receptor (HER1) activities and their downstream signaling pathways, Akt, extracellular-signal-regulated kinase (ERK1/2), and signal transducers and activators of transcription (STAT) 5b, as well as on cell migration in a human breast cancer cell line, MDA-MB-231. We also investigated whether the AhR is involved in HCB-induced effects. We have demonstrated that HCB (0.05μM) produces an early increase of Y416-c-Src, Y845-HER1, Y699-STAT5b, and ERK1/2 phosphorylation. Moreover, our results have shown that the pesticide (15 min) activates these pathways in a dose-dependent manner (0.005, 0.05, 0.5, and 5μM). In contrast, HCB does not alter T308-Akt activation. Pretreatment with a specific inhibitor for c-Src (4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d]pyrimidine [PP2]) prevents Y845-HER1 and Y699-STAT5b phosphorylation. AG1478, a specific HER1 inhibitor, abrogates HCB-induced STAT5b and ERK1/2 activation, whereas 4,7-orthophenanthroline and α-naphthoflavone, two AhR antagonists, prevent HCB-induced STAT5b and ERK1/2 phosphorylation. HCB enhances cell migration evaluated by scratch motility and transwell assays. Pretreatment with PP2, AG1478, and 4,7-orthophenanthroline suppresses HCB-induced cell migration. These results demonstrate that HCB stimulates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways in MDA-MB-231. c-Src, HER1, and AhR are involved in HCB-induced increase in cell migration. The present study makes a significant contribution to the molecular mechanism of action of HCB in mammary carcinogenesis.
publishDate 2011
dc.date.none.fl_str_mv 2011-04
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/11336/113525
Pontillo, Carolina Andrea; García, María A.; Peña, Delfina; Cocca, Claudia Marcela; Chiappini, Florencia Ana; et al.; Activation of c-Src/HER1/STAT5b and HER1/ERK1/2 Signaling Pathways and Cell Migration by Hexachlorobenzene in MDA-MB-231 Human Breast Cancer Cell Line; Oxford University Press; Toxicological Sciences; 120; 2; 4-2011; 284-296
1096-6080
CONICET Digital
CONICET
url http://hdl.handle.net/11336/113525
identifier_str_mv Pontillo, Carolina Andrea; García, María A.; Peña, Delfina; Cocca, Claudia Marcela; Chiappini, Florencia Ana; et al.; Activation of c-Src/HER1/STAT5b and HER1/ERK1/2 Signaling Pathways and Cell Migration by Hexachlorobenzene in MDA-MB-231 Human Breast Cancer Cell Line; Oxford University Press; Toxicological Sciences; 120; 2; 4-2011; 284-296
1096-6080
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1093/toxsci/kfq390
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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 13.10058

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