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Constitutive expression of Bcl-2 induces epithelial-Mesenchymal transition in mammary epithelial cells

BACKGROUND: Bcl-2 (B cell lymphoma/leukemia gene-2) is the first proto-oncogene recognized to function by inhibiting programmed cell death/apoptosis. Although much is known about the anti-apoptotic ability of Bcl-2, little information is available concerning its function in other cellular processes,...

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Autores principales: An, Juan, Lv, Jin, Li, Aimin, Qiao, Junxiao, Fang, Liang, Li, Zhihua, Li, Bo, Zhao, Wei, Chen, Huoming, Wang, Liying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4475317/
https://www.ncbi.nlm.nih.gov/pubmed/26091803
http://dx.doi.org/10.1186/s12885-015-1485-5
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author An, Juan
Lv, Jin
Li, Aimin
Qiao, Junxiao
Fang, Liang
Li, Zhihua
Li, Bo
Zhao, Wei
Chen, Huoming
Wang, Liying
author_facet An, Juan
Lv, Jin
Li, Aimin
Qiao, Junxiao
Fang, Liang
Li, Zhihua
Li, Bo
Zhao, Wei
Chen, Huoming
Wang, Liying
author_sort An, Juan
collection PubMed
description BACKGROUND: Bcl-2 (B cell lymphoma/leukemia gene-2) is the first proto-oncogene recognized to function by inhibiting programmed cell death/apoptosis. Although much is known about the anti-apoptotic ability of Bcl-2, little information is available concerning its function in other cellular processes, such as cell differentiation. METHODS: In this study, stable cell lines from pre-malignant MCF10ATG3B mammary epithelial cells, a cell line derived from a human proliferative breast disease model, to express exogenous Bcl-2 was established. CMV promoter driven Bcl-2 expression vector or empty vector was transfected into MCF10ATG3B human mammary epithelial cells to investigate the effects of Bcl-2 on mammary epithelial cells. In addition, western blot and immunofluoresence staining were employed to testify the marker proteins of both mesenchymal and epithelial cells. RESULTS: Unexpectedly, a dramatic change of phenotype from epithelial cells to fibroblast-like cells was observed in Bcl-2-transfected cells. Western blot analysis and immunofluoresence staining results demonstrated that the E-cadherin and desmoplakin, markers of epithelial cells, were downregulated in the Bcl-2-transfected cells. However, N-cadherin and vimentin, markers of mesenchymal cells, were upregulated in these cells. Redistributions of cytokeratin and beta-catenin were also observed in the Bcl-2-transfected cells. Our results further showed that the Bcl-2-transfected MCF10ATG3B cells retained some epithelial markers, such as epithelial specific antigen (ESA) and epithelial membrane antigen (EMA), indicating their epithelial origin. In addition, cell migration and invasion was substantially increased in Bcl-2 transfected cells. CONCLUSION: Taken together, our results strongly indicate that in addition to its anti-apoptotic function, Bcl-2 is also involved in the epithelial-mesenchymal transition (EMT), a fundamental mechanism in normal morphogenesis and pathogenesis of some diseases.
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spelling pubmed-44753172015-06-21 Constitutive expression of Bcl-2 induces epithelial-Mesenchymal transition in mammary epithelial cells An, Juan Lv, Jin Li, Aimin Qiao, Junxiao Fang, Liang Li, Zhihua Li, Bo Zhao, Wei Chen, Huoming Wang, Liying BMC Cancer Research Article BACKGROUND: Bcl-2 (B cell lymphoma/leukemia gene-2) is the first proto-oncogene recognized to function by inhibiting programmed cell death/apoptosis. Although much is known about the anti-apoptotic ability of Bcl-2, little information is available concerning its function in other cellular processes, such as cell differentiation. METHODS: In this study, stable cell lines from pre-malignant MCF10ATG3B mammary epithelial cells, a cell line derived from a human proliferative breast disease model, to express exogenous Bcl-2 was established. CMV promoter driven Bcl-2 expression vector or empty vector was transfected into MCF10ATG3B human mammary epithelial cells to investigate the effects of Bcl-2 on mammary epithelial cells. In addition, western blot and immunofluoresence staining were employed to testify the marker proteins of both mesenchymal and epithelial cells. RESULTS: Unexpectedly, a dramatic change of phenotype from epithelial cells to fibroblast-like cells was observed in Bcl-2-transfected cells. Western blot analysis and immunofluoresence staining results demonstrated that the E-cadherin and desmoplakin, markers of epithelial cells, were downregulated in the Bcl-2-transfected cells. However, N-cadherin and vimentin, markers of mesenchymal cells, were upregulated in these cells. Redistributions of cytokeratin and beta-catenin were also observed in the Bcl-2-transfected cells. Our results further showed that the Bcl-2-transfected MCF10ATG3B cells retained some epithelial markers, such as epithelial specific antigen (ESA) and epithelial membrane antigen (EMA), indicating their epithelial origin. In addition, cell migration and invasion was substantially increased in Bcl-2 transfected cells. CONCLUSION: Taken together, our results strongly indicate that in addition to its anti-apoptotic function, Bcl-2 is also involved in the epithelial-mesenchymal transition (EMT), a fundamental mechanism in normal morphogenesis and pathogenesis of some diseases. BioMed Central 2015-06-20 /pmc/articles/PMC4475317/ /pubmed/26091803 http://dx.doi.org/10.1186/s12885-015-1485-5 Text en © An et al. 2015 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
An, Juan
Lv, Jin
Li, Aimin
Qiao, Junxiao
Fang, Liang
Li, Zhihua
Li, Bo
Zhao, Wei
Chen, Huoming
Wang, Liying
Constitutive expression of Bcl-2 induces epithelial-Mesenchymal transition in mammary epithelial cells
title Constitutive expression of Bcl-2 induces epithelial-Mesenchymal transition in mammary epithelial cells
title_full Constitutive expression of Bcl-2 induces epithelial-Mesenchymal transition in mammary epithelial cells
title_fullStr Constitutive expression of Bcl-2 induces epithelial-Mesenchymal transition in mammary epithelial cells
title_full_unstemmed Constitutive expression of Bcl-2 induces epithelial-Mesenchymal transition in mammary epithelial cells
title_short Constitutive expression of Bcl-2 induces epithelial-Mesenchymal transition in mammary epithelial cells
title_sort constitutive expression of bcl-2 induces epithelial-mesenchymal transition in mammary epithelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4475317/
https://www.ncbi.nlm.nih.gov/pubmed/26091803
http://dx.doi.org/10.1186/s12885-015-1485-5
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