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E4F1 deficiency results in oxidative stress–mediated cell death of leukemic cells

The multifunctional E4F1 protein was originally discovered as a target of the E1A viral oncoprotein. Growing evidence indicates that E4F1 is involved in key signaling pathways commonly deregulated during cell transformation. In this study, we investigate the influence of E4F1 on tumorigenesis. Wild-...

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Autores principales: Hatchi, Elodie, Rodier, Genevieve, Lacroix, Matthieu, Caramel, Julie, Kirsh, Olivier, Jacquet, Chantal, Schrepfer, Emilie, Lagarrigue, Sylviane, Linares, Laetitia Karine, Lledo, Gwendaline, Tondeur, Sylvie, Dubus, Pierre, Sardet, Claude, Le Cam, Laurent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135361/
https://www.ncbi.nlm.nih.gov/pubmed/21708927
http://dx.doi.org/10.1084/jem.20101995
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author Hatchi, Elodie
Rodier, Genevieve
Lacroix, Matthieu
Caramel, Julie
Kirsh, Olivier
Jacquet, Chantal
Schrepfer, Emilie
Lagarrigue, Sylviane
Linares, Laetitia Karine
Lledo, Gwendaline
Tondeur, Sylvie
Dubus, Pierre
Sardet, Claude
Le Cam, Laurent
author_facet Hatchi, Elodie
Rodier, Genevieve
Lacroix, Matthieu
Caramel, Julie
Kirsh, Olivier
Jacquet, Chantal
Schrepfer, Emilie
Lagarrigue, Sylviane
Linares, Laetitia Karine
Lledo, Gwendaline
Tondeur, Sylvie
Dubus, Pierre
Sardet, Claude
Le Cam, Laurent
author_sort Hatchi, Elodie
collection PubMed
description The multifunctional E4F1 protein was originally discovered as a target of the E1A viral oncoprotein. Growing evidence indicates that E4F1 is involved in key signaling pathways commonly deregulated during cell transformation. In this study, we investigate the influence of E4F1 on tumorigenesis. Wild-type mice injected with fetal liver cells from mice lacking CDKN2A, the gene encoding Ink4a/Arf, developed histiocytic sarcomas (HSs), a tumor originating from the monocytic/macrophagic lineage. Cre-mediated deletion of E4F1 resulted in the death of HS cells and tumor regression in vivo and extended the lifespan of recipient animals. In murine and human HS cell lines, E4F1 inactivation resulted in mitochondrial defects and increased production of reactive oxygen species (ROS) that triggered massive cell death. Notably, these defects of E4F1 depletion were observed in HS cells but not healthy primary macrophages. Short hairpin RNA–mediated depletion of E4F1 induced mitochondrial defects and ROS-mediated death in several human myeloid leukemia cell lines. E4F1 protein is overexpressed in a large subset of human acute myeloid leukemia samples. Together, these data reveal a role for E4F1 in the survival of myeloid leukemic cells and support the notion that targeting E4F1 activities might have therapeutic interest.
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spelling pubmed-31353612012-01-04 E4F1 deficiency results in oxidative stress–mediated cell death of leukemic cells Hatchi, Elodie Rodier, Genevieve Lacroix, Matthieu Caramel, Julie Kirsh, Olivier Jacquet, Chantal Schrepfer, Emilie Lagarrigue, Sylviane Linares, Laetitia Karine Lledo, Gwendaline Tondeur, Sylvie Dubus, Pierre Sardet, Claude Le Cam, Laurent J Exp Med Article The multifunctional E4F1 protein was originally discovered as a target of the E1A viral oncoprotein. Growing evidence indicates that E4F1 is involved in key signaling pathways commonly deregulated during cell transformation. In this study, we investigate the influence of E4F1 on tumorigenesis. Wild-type mice injected with fetal liver cells from mice lacking CDKN2A, the gene encoding Ink4a/Arf, developed histiocytic sarcomas (HSs), a tumor originating from the monocytic/macrophagic lineage. Cre-mediated deletion of E4F1 resulted in the death of HS cells and tumor regression in vivo and extended the lifespan of recipient animals. In murine and human HS cell lines, E4F1 inactivation resulted in mitochondrial defects and increased production of reactive oxygen species (ROS) that triggered massive cell death. Notably, these defects of E4F1 depletion were observed in HS cells but not healthy primary macrophages. Short hairpin RNA–mediated depletion of E4F1 induced mitochondrial defects and ROS-mediated death in several human myeloid leukemia cell lines. E4F1 protein is overexpressed in a large subset of human acute myeloid leukemia samples. Together, these data reveal a role for E4F1 in the survival of myeloid leukemic cells and support the notion that targeting E4F1 activities might have therapeutic interest. The Rockefeller University Press 2011-07-04 /pmc/articles/PMC3135361/ /pubmed/21708927 http://dx.doi.org/10.1084/jem.20101995 Text en © 2011 Hatchi et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Hatchi, Elodie
Rodier, Genevieve
Lacroix, Matthieu
Caramel, Julie
Kirsh, Olivier
Jacquet, Chantal
Schrepfer, Emilie
Lagarrigue, Sylviane
Linares, Laetitia Karine
Lledo, Gwendaline
Tondeur, Sylvie
Dubus, Pierre
Sardet, Claude
Le Cam, Laurent
E4F1 deficiency results in oxidative stress–mediated cell death of leukemic cells
title E4F1 deficiency results in oxidative stress–mediated cell death of leukemic cells
title_full E4F1 deficiency results in oxidative stress–mediated cell death of leukemic cells
title_fullStr E4F1 deficiency results in oxidative stress–mediated cell death of leukemic cells
title_full_unstemmed E4F1 deficiency results in oxidative stress–mediated cell death of leukemic cells
title_short E4F1 deficiency results in oxidative stress–mediated cell death of leukemic cells
title_sort e4f1 deficiency results in oxidative stress–mediated cell death of leukemic cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135361/
https://www.ncbi.nlm.nih.gov/pubmed/21708927
http://dx.doi.org/10.1084/jem.20101995
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