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Artículo

Non-genomic actions of estradiol and 4-OH-tamoxifen on murine breast cancer cells

Raffo, Diego AlejandroIcon ; Pontiggia, Osvaldo AlejandroIcon ; Bal, Elisa DoraIcon ; Simian, MarinaIcon
Fecha de publicación: 01/2015
Editorial: Spandidos Publications
Revista: Oncology Reports
ISSN: 1021-335X
e-ISSN: 1791-2431
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Inmunología

Resumen

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.
Palabras clave: Breast Cancer , Estradiol , Tamoxifen , Non Genomic Pathways , Non Genomic Signaling
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/37886
DOI: http://dx.doi.org/10.3892/or.2014.3558
URL: https://www.spandidos-publications.com/or/33/1/439
Colecciones
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
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
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