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dc.contributor.author
Raffo, Diego Alejandro
dc.contributor.author
Pontiggia, Osvaldo Alejandro
dc.contributor.author
Bal, Elisa Dora
dc.contributor.author
Simian, Marina
dc.date.available
2018-03-05T19:40:50Z
dc.date.issued
2015-01
dc.identifier.citation
Raffo, Diego Alejandro; Pontiggia, Osvaldo Alejandro; Bal, Elisa Dora; Simian, Marina; Non-genomic actions of estradiol and 4-OH-tamoxifen on murine breast cancer cells; Spandidos Publications; Oncology Reports; 33; 1; 1-2015; 439-447
dc.identifier.issn
1021-335X
dc.identifier.uri
http://hdl.handle.net/11336/37886
dc.description.abstract
Estrogens and tamoxifen do not only exert their effects at the genomic level, but also play a role at the cell membrane activating downstream signaling pathways. We recently characterized an estrogen receptor-positive epithelial murine breast cancer cell line, LM05-E. Utilizing this cell line and MCF-7 cells, we compared the non-genomic effects of estradiol and 4-OH-tamoxifen. We showed that, similar to estradiol, tamoxifen activated the MAPK/ERK 1/2 pathway; however, we did not find activation of PI3K/AKT by either estradiol or tamoxifen. Short-term treatments with estradiol stimulated, whereas tamoxifen inhibited cell proliferation. Using pharmacological inhibitors we showed that the effect of estradiol was mediated by the MAPK/ERK 1/2 pathway, but that inhibition of this pathway did not affect tamoxifen. Surprisingly, however, blocking of PI3K/AKT signaling interfered with the inhibitory effect of tamoxifen. Analysis of the involvement of the EGFR support previous findings that designate this receptor as a mediator of the non-genomic effects of estradiol; blocking EGFR also reverses the inhibitory effect of tamoxifen. Finally, matrix metalloproteinases (MMPs) were confirmed to be involved in the proliferative effect of estradiol. These results demonstrated the novel non-genomic effects of tamoxifen and revealed that pathways downstream of EGFR and PI3K/AKT are involved in the inhibition of cell proliferation. Caution should be exercised when analyzing strategies that aim at combining endocrine therapy with specific signaling inhibitors.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Spandidos Publications
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Breast Cancer
dc.subject
Estradiol
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Tamoxifen
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Non Genomic Pathways
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Non Genomic Signaling
dc.subject.classification
Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Non-genomic actions of estradiol and 4-OH-tamoxifen on murine breast cancer cells
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-03-02T14:02:22Z
dc.identifier.eissn
1791-2431
dc.journal.volume
33
dc.journal.number
1
dc.journal.pagination
439-447
dc.journal.pais
Grecia
dc.journal.ciudad
Atenas
dc.description.fil
Fil: Raffo, Diego Alejandro. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Pontiggia, Osvaldo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
dc.description.fil
Fil: Bal, Elisa Dora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
dc.description.fil
Fil: Simian, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
dc.journal.title
Oncology Reports
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3892/or.2014.3558
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.spandidos-publications.com/or/33/1/439


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