Non-genomic actions of estradiol and 4-OH-tamoxifen on murine breast cancer cells
| Autor: | Marina Simian, Elisa Bal de Kier Joffé, Osvaldo Pontiggia, Diego Raffo |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
MAPK/ERK pathway
Cancer Research CIENCIAS MÉDICAS Y DE LA SALUD medicine.drug_class Cell Inmunología Breast Neoplasms Biology Mice Phosphatidylinositol 3-Kinases BREAST CANCER Cell Line Tumor medicine Animals Humans TAMOXIFEN skin and connective tissue diseases Extracellular Signal-Regulated MAP Kinases Protein kinase B ESTRADIOL PI3K/AKT/mTOR pathway Cell Proliferation NON GENOMIC PATHWAYS Estradiol Cell growth General Medicine Cell cycle Tyrphostins ErbB Receptors Medicina Básica Tamoxifen medicine.anatomical_structure Oncology Estrogen Cancer research MCF-7 Cells Quinazolines Female NON GENOMIC SIGNALING Proto-Oncogene Proteins c-akt hormones hormone substitutes and hormone antagonists medicine.drug Signal Transduction |
| Zdroj: | Oncology reports. 33(1) |
| ISSN: | 1791-2431 |
| Popis: | 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. Fil: Raffo, Diego Alejandro. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Pontiggia, Osvaldo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina Fil: Bal, Elisa Dora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina Fil: Simian, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina |
| Databáze: | OpenAIRE |
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