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Myocyte Enhancer Factor 2C as a New Player in Human Breast Cancer Brain Metastases
Myocyte enhancer factor 2C (MEF2C) is increasingly expressed in mice along with breast cancer brain metastases (BCBM) development. We aim to ascertain MEF2C expression in human BCBM, establish the relationship with disease severity, disclose the involvement of vascular endothelial growth factor rece...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917785/ https://www.ncbi.nlm.nih.gov/pubmed/33673112 http://dx.doi.org/10.3390/cells10020378 |
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author | Galego, Sofia Kauppila, Linda Azevedo Malhó, Rui Pimentel, José Brito, Maria Alexandra |
author_facet | Galego, Sofia Kauppila, Linda Azevedo Malhó, Rui Pimentel, José Brito, Maria Alexandra |
author_sort | Galego, Sofia |
collection | PubMed |
description | Myocyte enhancer factor 2C (MEF2C) is increasingly expressed in mice along with breast cancer brain metastases (BCBM) development. We aim to ascertain MEF2C expression in human BCBM, establish the relationship with disease severity, disclose the involvement of vascular endothelial growth factor receptor-2 (VEGFR-2) and β-catenin, also known as KDR and CTNNB1, respectively, and investigate if matched primary tumors express the protein. We studied resected BCBM for the expression of MEF2C, VEGFR-2, and ß-catenin, as well as proliferation (Ki-67) and epithelial (pan Cytokeratin) markers, and related experimental and clinical data. MEF2C expression was further assessed in matched primary tumors and non-BCBM samples used as controls. MEF2C expression was observed in BCBM, but not in controls, and was categorized into three phenotypes (P): P1, with extranuclear location; P2, with extranuclear and nuclear staining, and P3, with nuclear location. Nuclear translocation increased with metastases extension and Ki-67-positive cells number. P1 was associated with higher VEFGR-2 plasma membrane immunoreactivity, whereas P2 and P3 were accompanied by protein dislocation. P1 was accompanied by β-catenin membrane expression, while P2 and P3 exhibited β-catenin nuclear translocation. Primary BC samples expressed MEF2C in mammary ducts and scattered cells in the parenchyma. MEF2C emerges as a player in BCBM associated with disease severity and VEGFR-2 and β-catenin signaling. |
format | Online Article Text |
id | pubmed-7917785 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79177852021-03-02 Myocyte Enhancer Factor 2C as a New Player in Human Breast Cancer Brain Metastases Galego, Sofia Kauppila, Linda Azevedo Malhó, Rui Pimentel, José Brito, Maria Alexandra Cells Article Myocyte enhancer factor 2C (MEF2C) is increasingly expressed in mice along with breast cancer brain metastases (BCBM) development. We aim to ascertain MEF2C expression in human BCBM, establish the relationship with disease severity, disclose the involvement of vascular endothelial growth factor receptor-2 (VEGFR-2) and β-catenin, also known as KDR and CTNNB1, respectively, and investigate if matched primary tumors express the protein. We studied resected BCBM for the expression of MEF2C, VEGFR-2, and ß-catenin, as well as proliferation (Ki-67) and epithelial (pan Cytokeratin) markers, and related experimental and clinical data. MEF2C expression was further assessed in matched primary tumors and non-BCBM samples used as controls. MEF2C expression was observed in BCBM, but not in controls, and was categorized into three phenotypes (P): P1, with extranuclear location; P2, with extranuclear and nuclear staining, and P3, with nuclear location. Nuclear translocation increased with metastases extension and Ki-67-positive cells number. P1 was associated with higher VEFGR-2 plasma membrane immunoreactivity, whereas P2 and P3 were accompanied by protein dislocation. P1 was accompanied by β-catenin membrane expression, while P2 and P3 exhibited β-catenin nuclear translocation. Primary BC samples expressed MEF2C in mammary ducts and scattered cells in the parenchyma. MEF2C emerges as a player in BCBM associated with disease severity and VEGFR-2 and β-catenin signaling. MDPI 2021-02-12 /pmc/articles/PMC7917785/ /pubmed/33673112 http://dx.doi.org/10.3390/cells10020378 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Galego, Sofia Kauppila, Linda Azevedo Malhó, Rui Pimentel, José Brito, Maria Alexandra Myocyte Enhancer Factor 2C as a New Player in Human Breast Cancer Brain Metastases |
title | Myocyte Enhancer Factor 2C as a New Player in Human Breast Cancer Brain Metastases |
title_full | Myocyte Enhancer Factor 2C as a New Player in Human Breast Cancer Brain Metastases |
title_fullStr | Myocyte Enhancer Factor 2C as a New Player in Human Breast Cancer Brain Metastases |
title_full_unstemmed | Myocyte Enhancer Factor 2C as a New Player in Human Breast Cancer Brain Metastases |
title_short | Myocyte Enhancer Factor 2C as a New Player in Human Breast Cancer Brain Metastases |
title_sort | myocyte enhancer factor 2c as a new player in human breast cancer brain metastases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917785/ https://www.ncbi.nlm.nih.gov/pubmed/33673112 http://dx.doi.org/10.3390/cells10020378 |
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