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dc.contributor.author
Papadimitropoulou, Adriana
dc.contributor.author
Vellón, Luciano
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dc.contributor.author
Atlas, Ella
dc.contributor.author
Steen, Travis Vander
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Cuyàs, Elisabet
dc.contributor.author
Verdura, Sara
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Espinoza, Ingrid
dc.contributor.author
Menendez, Javier A.
dc.contributor.author
Lupu, Ruth
dc.date.available
2021-05-24T20:01:37Z
dc.date.issued
2020-10
dc.identifier.citation
Papadimitropoulou, Adriana; Vellón, Luciano; Atlas, Ella; Steen, Travis Vander; Cuyàs, Elisabet; et al.; Heregulin drives endocrine resistance by altering il-8 expression in er-positive breast cancer; MDPI AG; International Journal of Molecular Sciences; 21; 20; 10-2020; 1-15
dc.identifier.issn
1661-6596
dc.identifier.uri
http://hdl.handle.net/11336/132525
dc.description.abstract
Sustained HER2/HER3 signaling due to the overproduction of the HER3 ligand heregulin (HRG) is proposed as a key contributor to endocrine resistance in estrogen receptor-positive (ER+) breast cancer. The molecular mechanisms linking HER2 transactivation by HRG-bound HER3 to the acquisition of a hormone-independent phenotype in ER+ breast cancer is, however, largely unknown. Here, we explored the possibility that autocrine HRG signaling drives cytokine-related endocrine resistance in ER+ breast cancer cells. We used human cytokine antibody arrays to semi-quantitatively measure the expression level of 60 cytokines and growth factors in the extracellular milieu of MCF-7 cells engineered to overexpress full-length HRGβ2 (MCF-7/HRG cells). Interleukin-8 (IL-8), a chemokine closely linked to ER inaction, emerged as one the most differentially expressed cytokines. Cytokine profiling using structural deletion mutants lacking both the N-terminus and the cytoplasmic-transmembrane region of HRGβ2—which is not secreted and cannot transactivate HER2—or lacking a nuclear localization signal at the N-terminus—which cannot localize at the nucleus but is actively secreted and transactivates HER2—revealed that the HRG-driven activation of IL-8 expression in ER+ cells required HRG secretion and transactivation of HER2 but not HRG nuclear localization. The functional blockade of IL-8 with a specific antibody inversely regulated ERα-driven transcriptional activation in endocrine-sensitive MCF-7 cells and endocrine-resistant MCF-7/HRG cells. Overall, these findings suggest that IL-8 participates in the HRG-driven endocrine resistance program in ER+/HER2- breast cancer and might illuminate a potential clinical setting for IL8- or CXCR1/2-neutralizing antibodies.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
MDPI AG
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
AUTOCRINE
dc.subject
CYTOKINES
dc.subject
IL-8
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LUMINAL
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TAMOXIFEN
dc.subject.classification
Biología Celular, Microbiología
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Heregulin drives endocrine resistance by altering il-8 expression in er-positive breast cancer
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2021-04-22T20:06:25Z
dc.identifier.eissn
1422-0067
dc.journal.volume
21
dc.journal.number
20
dc.journal.pagination
1-15
dc.journal.pais
Países Bajos
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dc.description.fil
Fil: Papadimitropoulou, Adriana. Academy of Athens; Grecia
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Fil: Vellón, Luciano. 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
dc.description.fil
Fil: Atlas, Ella. University of Ottawa; Canadá
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Fil: Steen, Travis Vander. Mayo Clinic; Estados Unidos
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Fil: Cuyàs, Elisabet. Institut D'investigació Biomèdica de Girona Dr. Josep Trueta; España. Institut Català d'Oncologia; España
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Fil: Verdura, Sara. Institut Català d'Oncologia; España. Institut D'investigació Biomèdica de Girona Dr. Josep Trueta; España
dc.description.fil
Fil: Espinoza, Ingrid. University of Mississippi; Estados Unidos
dc.description.fil
Fil: Menendez, Javier A.. Institut Català d'Oncologia; España. Institut D'investigació Biomèdica de Girona Dr. Josep Trueta; España
dc.description.fil
Fil: Lupu, Ruth. Mayo Clinic; Estados Unidos. University of Ottawa; Canadá. Mayo Clinic Cancer Center; Estados Unidos
dc.journal.title
International Journal of Molecular Sciences
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/21/20/7737
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3390/ijms21207737
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