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dc.contributor.author
Pontillo, Carolina Andrea
dc.contributor.author
García, María A.
dc.contributor.author
Peña, Delfina
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Cocca, Claudia Marcela
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Chiappini, Florencia Ana
dc.contributor.author
Alvarez, Laura
dc.contributor.author
Kleiman, Diana Leonor
dc.contributor.author
Randi, Andrea Silvana
dc.date.available
2020-09-08T18:01:33Z
dc.date.issued
2011-04
dc.identifier.citation
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
dc.identifier.issn
1096-6080
dc.identifier.uri
http://hdl.handle.net/11336/113525
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Oxford University Press
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Hexaclorobenceno
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AhR
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MDA-MB-231
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c-Src
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Otras Ciencias de la Salud
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Ciencias de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.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
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-09-03T16:56:52Z
dc.journal.volume
120
dc.journal.number
2
dc.journal.pagination
284-296
dc.journal.pais
Reino Unido
dc.journal.ciudad
Oxford
dc.description.fil
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
dc.description.fil
Fil: García, María A.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.journal.title
Toxicological Sciences
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kfq390
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1093/toxsci/kfq390
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