Bcl-XL mediates epidermal growth factor dependent cell survival in HC11 mammary epithelial cells
Apoptosis is the predominant process controlling cell deletion during post-lactational mammary gland remodeling. The members of the Bcl-2 protein family, whose expression levels are under the control of lactogenic hormones, internally control this mechanism. Epidermal growth factor (EGF) belongs to...
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Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_01674889_v1793_n3_p496_Romorini |
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paperaa:paper_01674889_v1793_n3_p496_Romorini2023-06-12T16:46:58Z Bcl-XL mediates epidermal growth factor dependent cell survival in HC11 mammary epithelial cells Biochim. Biophys. Acta Mol. Cell Res. 2009;1793(3):496-505 Romorini, L. Coso, O.A. Pecci, A. Apoptosis Bad Bcl-XL EGF Mammary epithelial cell MAPKs cytochrome c mitogen activated protein kinase 1 mitogen activated protein kinase 3 phosphatidylinositol 3 kinase protein BAD protein bcl 2 protein bcl xl protein kinase B recombinant epidermal growth factor stress activated protein kinase cytochrome c epidermal growth factor phosphatidylinositol 3 kinase protein BAD protein bcl x protein kinase B stress activated protein kinase animal cell apoptosis article breast epithelium cell survival controlled study down regulation enzyme activation epithelium cell mitochondrion mouse nonhuman priority journal protein expression protein family protein induction protein phosphorylation protein secretion signal transduction animal cell survival epithelium cell female genetics human metabolism phosphorylation udder 1-Phosphatidylinositol 3-Kinase Animals Apoptosis bcl-Associated Death Protein bcl-X Protein Cell Survival Cytochromes c Down-Regulation Epidermal Growth Factor Epithelial Cells Female Humans JNK Mitogen-Activated Protein Kinases Mammary Glands, Animal Mice Mitochondria Phosphorylation Proto-Oncogene Proteins c-akt Apoptosis is the predominant process controlling cell deletion during post-lactational mammary gland remodeling. The members of the Bcl-2 protein family, whose expression levels are under the control of lactogenic hormones, internally control this mechanism. Epidermal growth factor (EGF) belongs to a family of proteins that act as survival factors for mammary epithelial cells upon binding to specific membrane tyrosine kinase receptors. Expression of EGF peaks during lactation and dramatically decreases in the involuting mammary gland. Though it was suggested that the protective effect of EGF is mediated through the phosphatidylinositol-3-kinase (PI3K) or MEK/ERK kinases activities, little is known about the downstream mechanisms involved on the anti-apoptotic effect of EGF on mammary epithelial cells; particularly the identity of target genes controlling apoptosis. Here, we focused on the effect of EGF on the survival of mammary epithelial cells. We particularly aimed at the characterization of the signaling pathways that were triggered by this growth factor, impinge upon expression of Bcl-2 family members and therefore have an impact on the regulation of cell survival. We demonstrate that EGF provokes the induction of the anti-apoptotic isoform Bcl-XL and the phosphorylation and down-regulation of the pro-apoptotic protein Bad. The activation of JNK and PI3K/AKT signaling pathways promotes the induction of Bcl-XL while AKT activation also leads to Bad phosphorylation and down-regulation. This protective effect of EGF correlates mainly with the up-regulation of Bcl-XL than with the down-regulation of Bad. In fact, HC11 cells unable to express bcl-X, die even in the presence of EGF. In this context, Bcl-XL emerges as a key anti-apoptotic molecule critical for mediating EGF cell survival. © 2008 Elsevier B.V. All rights reserved. Fil:Romorini, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Coso, O.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pecci, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2009 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_01674889_v1793_n3_p496_Romorini |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
language |
Inglés |
orig_language_str_mv |
eng |
topic |
Apoptosis Bad Bcl-XL EGF Mammary epithelial cell MAPKs cytochrome c mitogen activated protein kinase 1 mitogen activated protein kinase 3 phosphatidylinositol 3 kinase protein BAD protein bcl 2 protein bcl xl protein kinase B recombinant epidermal growth factor stress activated protein kinase cytochrome c epidermal growth factor phosphatidylinositol 3 kinase protein BAD protein bcl x protein kinase B stress activated protein kinase animal cell apoptosis article breast epithelium cell survival controlled study down regulation enzyme activation epithelium cell mitochondrion mouse nonhuman priority journal protein expression protein family protein induction protein phosphorylation protein secretion signal transduction animal cell survival epithelium cell female genetics human metabolism phosphorylation udder 1-Phosphatidylinositol 3-Kinase Animals Apoptosis bcl-Associated Death Protein bcl-X Protein Cell Survival Cytochromes c Down-Regulation Epidermal Growth Factor Epithelial Cells Female Humans JNK Mitogen-Activated Protein Kinases Mammary Glands, Animal Mice Mitochondria Phosphorylation Proto-Oncogene Proteins c-akt |
spellingShingle |
Apoptosis Bad Bcl-XL EGF Mammary epithelial cell MAPKs cytochrome c mitogen activated protein kinase 1 mitogen activated protein kinase 3 phosphatidylinositol 3 kinase protein BAD protein bcl 2 protein bcl xl protein kinase B recombinant epidermal growth factor stress activated protein kinase cytochrome c epidermal growth factor phosphatidylinositol 3 kinase protein BAD protein bcl x protein kinase B stress activated protein kinase animal cell apoptosis article breast epithelium cell survival controlled study down regulation enzyme activation epithelium cell mitochondrion mouse nonhuman priority journal protein expression protein family protein induction protein phosphorylation protein secretion signal transduction animal cell survival epithelium cell female genetics human metabolism phosphorylation udder 1-Phosphatidylinositol 3-Kinase Animals Apoptosis bcl-Associated Death Protein bcl-X Protein Cell Survival Cytochromes c Down-Regulation Epidermal Growth Factor Epithelial Cells Female Humans JNK Mitogen-Activated Protein Kinases Mammary Glands, Animal Mice Mitochondria Phosphorylation Proto-Oncogene Proteins c-akt Romorini, L. Coso, O.A. Pecci, A. Bcl-XL mediates epidermal growth factor dependent cell survival in HC11 mammary epithelial cells |
topic_facet |
Apoptosis Bad Bcl-XL EGF Mammary epithelial cell MAPKs cytochrome c mitogen activated protein kinase 1 mitogen activated protein kinase 3 phosphatidylinositol 3 kinase protein BAD protein bcl 2 protein bcl xl protein kinase B recombinant epidermal growth factor stress activated protein kinase cytochrome c epidermal growth factor phosphatidylinositol 3 kinase protein BAD protein bcl x protein kinase B stress activated protein kinase animal cell apoptosis article breast epithelium cell survival controlled study down regulation enzyme activation epithelium cell mitochondrion mouse nonhuman priority journal protein expression protein family protein induction protein phosphorylation protein secretion signal transduction animal cell survival epithelium cell female genetics human metabolism phosphorylation udder 1-Phosphatidylinositol 3-Kinase Animals Apoptosis bcl-Associated Death Protein bcl-X Protein Cell Survival Cytochromes c Down-Regulation Epidermal Growth Factor Epithelial Cells Female Humans JNK Mitogen-Activated Protein Kinases Mammary Glands, Animal Mice Mitochondria Phosphorylation Proto-Oncogene Proteins c-akt |
description |
Apoptosis is the predominant process controlling cell deletion during post-lactational mammary gland remodeling. The members of the Bcl-2 protein family, whose expression levels are under the control of lactogenic hormones, internally control this mechanism. Epidermal growth factor (EGF) belongs to a family of proteins that act as survival factors for mammary epithelial cells upon binding to specific membrane tyrosine kinase receptors. Expression of EGF peaks during lactation and dramatically decreases in the involuting mammary gland. Though it was suggested that the protective effect of EGF is mediated through the phosphatidylinositol-3-kinase (PI3K) or MEK/ERK kinases activities, little is known about the downstream mechanisms involved on the anti-apoptotic effect of EGF on mammary epithelial cells; particularly the identity of target genes controlling apoptosis. Here, we focused on the effect of EGF on the survival of mammary epithelial cells. We particularly aimed at the characterization of the signaling pathways that were triggered by this growth factor, impinge upon expression of Bcl-2 family members and therefore have an impact on the regulation of cell survival. We demonstrate that EGF provokes the induction of the anti-apoptotic isoform Bcl-XL and the phosphorylation and down-regulation of the pro-apoptotic protein Bad. The activation of JNK and PI3K/AKT signaling pathways promotes the induction of Bcl-XL while AKT activation also leads to Bad phosphorylation and down-regulation. This protective effect of EGF correlates mainly with the up-regulation of Bcl-XL than with the down-regulation of Bad. In fact, HC11 cells unable to express bcl-X, die even in the presence of EGF. In this context, Bcl-XL emerges as a key anti-apoptotic molecule critical for mediating EGF cell survival. © 2008 Elsevier B.V. All rights reserved. |
format |
Artículo Artículo publishedVersion |
author |
Romorini, L. Coso, O.A. Pecci, A. |
author_facet |
Romorini, L. Coso, O.A. Pecci, A. |
author_sort |
Romorini, L. |
title |
Bcl-XL mediates epidermal growth factor dependent cell survival in HC11 mammary epithelial cells |
title_short |
Bcl-XL mediates epidermal growth factor dependent cell survival in HC11 mammary epithelial cells |
title_full |
Bcl-XL mediates epidermal growth factor dependent cell survival in HC11 mammary epithelial cells |
title_fullStr |
Bcl-XL mediates epidermal growth factor dependent cell survival in HC11 mammary epithelial cells |
title_full_unstemmed |
Bcl-XL mediates epidermal growth factor dependent cell survival in HC11 mammary epithelial cells |
title_sort |
bcl-xl mediates epidermal growth factor dependent cell survival in hc11 mammary epithelial cells |
publishDate |
2009 |
url |
http://hdl.handle.net/20.500.12110/paper_01674889_v1793_n3_p496_Romorini |
work_keys_str_mv |
AT romorinil bclxlmediatesepidermalgrowthfactordependentcellsurvivalinhc11mammaryepithelialcells AT cosooa bclxlmediatesepidermalgrowthfactordependentcellsurvivalinhc11mammaryepithelialcells AT peccia bclxlmediatesepidermalgrowthfactordependentcellsurvivalinhc11mammaryepithelialcells |
_version_ |
1769810114159575040 |