Estradiol Induces Epithelial to Mesenchymal Transition of Human Glioblastoma Cells
The mesenchymal phenotype of glioblastoma multiforme (GBM), the most frequent and malignant brain tumor, is associated with the worst prognosis. The epithelial–mesenchymal transition (EMT) is a cell plasticity mechanism involved in GBM malignancy. In this study, we determined 17β-estradiol (E2)-indu...
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MDPI AG
2020-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/9/1930 |
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| author | Ana M. Hernández-Vega Aylin Del Moral-Morales Carmen J. Zamora-Sánchez Ana G. Piña-Medina Aliesha González-Arenas Ignacio Camacho-Arroyo |
| author_facet | Ana M. Hernández-Vega Aylin Del Moral-Morales Carmen J. Zamora-Sánchez Ana G. Piña-Medina Aliesha González-Arenas Ignacio Camacho-Arroyo |
| author_sort | Ana M. Hernández-Vega |
| collection | DOAJ |
| description | The mesenchymal phenotype of glioblastoma multiforme (GBM), the most frequent and malignant brain tumor, is associated with the worst prognosis. The epithelial–mesenchymal transition (EMT) is a cell plasticity mechanism involved in GBM malignancy. In this study, we determined 17β-estradiol (E2)-induced EMT by changes in cell morphology, expression of EMT markers, and cell migration and invasion assays in human GBM-derived cell lines. E2 (10 nM) modified the shape and size of GBM cells due to a reorganization of actin filaments. We evaluated EMT markers expression by RT-qPCR, Western blot, and immunofluorescence.We found that E2 upregulated the expression of the mesenchymal markers, vimentin, and N-cadherin. Scratch and transwell assays showed that E2 increased migration and invasion of GBM cells. The estrogen receptor-α (ER-α)-selective agonist 4,4’,4’’-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT, 10 nM) affected similarly to E2 in terms of the expression of EMT markers and cell migration, and the treatment with the ER-α antagonist methyl-piperidino-pyrazole (MPP, 1 μM) blocked E2 and PPT effects. ER-β-selective agonist diarylpropionitrile (DNP, 10 nM) and antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazole[1,5-a]pyrimidin-3-yl]phenol (PHTPP, 1 μM) showed no effects on EMT marker expression. These data suggest that E2 induces EMT activation through ER-α in human GBM-derived cells. |
| first_indexed | 2024-03-10T17:04:25Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T17:04:25Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-edd2b9144ed349a1a3692ef9adfe356c2023-11-20T10:51:54ZengMDPI AGCells2073-44092020-08-0199193010.3390/cells9091930Estradiol Induces Epithelial to Mesenchymal Transition of Human Glioblastoma CellsAna M. Hernández-Vega0Aylin Del Moral-Morales1Carmen J. Zamora-Sánchez2Ana G. Piña-Medina3Aliesha González-Arenas4Ignacio Camacho-Arroyo5Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México, México City CP 11000, MexicoUnidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México, México City CP 11000, MexicoUnidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México, México City CP 11000, MexicoDepartamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, México City CP 04510, MexicoDepartamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City CP 04510, MexicoUnidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México, México City CP 11000, MexicoThe mesenchymal phenotype of glioblastoma multiforme (GBM), the most frequent and malignant brain tumor, is associated with the worst prognosis. The epithelial–mesenchymal transition (EMT) is a cell plasticity mechanism involved in GBM malignancy. In this study, we determined 17β-estradiol (E2)-induced EMT by changes in cell morphology, expression of EMT markers, and cell migration and invasion assays in human GBM-derived cell lines. E2 (10 nM) modified the shape and size of GBM cells due to a reorganization of actin filaments. We evaluated EMT markers expression by RT-qPCR, Western blot, and immunofluorescence.We found that E2 upregulated the expression of the mesenchymal markers, vimentin, and N-cadherin. Scratch and transwell assays showed that E2 increased migration and invasion of GBM cells. The estrogen receptor-α (ER-α)-selective agonist 4,4’,4’’-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT, 10 nM) affected similarly to E2 in terms of the expression of EMT markers and cell migration, and the treatment with the ER-α antagonist methyl-piperidino-pyrazole (MPP, 1 μM) blocked E2 and PPT effects. ER-β-selective agonist diarylpropionitrile (DNP, 10 nM) and antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazole[1,5-a]pyrimidin-3-yl]phenol (PHTPP, 1 μM) showed no effects on EMT marker expression. These data suggest that E2 induces EMT activation through ER-α in human GBM-derived cells.https://www.mdpi.com/2073-4409/9/9/1930epithelial–mesenchymal transition (EMT)glioblastoma multiforme (GBM)17β-estradiol (E2)estrogen receptors (ERs) |
| spellingShingle | Ana M. Hernández-Vega Aylin Del Moral-Morales Carmen J. Zamora-Sánchez Ana G. Piña-Medina Aliesha González-Arenas Ignacio Camacho-Arroyo Estradiol Induces Epithelial to Mesenchymal Transition of Human Glioblastoma Cells Cells epithelial–mesenchymal transition (EMT) glioblastoma multiforme (GBM) 17β-estradiol (E2) estrogen receptors (ERs) |
| title | Estradiol Induces Epithelial to Mesenchymal Transition of Human Glioblastoma Cells |
| title_full | Estradiol Induces Epithelial to Mesenchymal Transition of Human Glioblastoma Cells |
| title_fullStr | Estradiol Induces Epithelial to Mesenchymal Transition of Human Glioblastoma Cells |
| title_full_unstemmed | Estradiol Induces Epithelial to Mesenchymal Transition of Human Glioblastoma Cells |
| title_short | Estradiol Induces Epithelial to Mesenchymal Transition of Human Glioblastoma Cells |
| title_sort | estradiol induces epithelial to mesenchymal transition of human glioblastoma cells |
| topic | epithelial–mesenchymal transition (EMT) glioblastoma multiforme (GBM) 17β-estradiol (E2) estrogen receptors (ERs) |
| url | https://www.mdpi.com/2073-4409/9/9/1930 |
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