Cargando…
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-...
Autores principales: | , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782208091969814528 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3135361 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT hatchielodie e4f1deficiencyresultsinoxidativestressmediatedcelldeathofleukemiccells AT rodiergenevieve e4f1deficiencyresultsinoxidativestressmediatedcelldeathofleukemiccells AT lacroixmatthieu e4f1deficiencyresultsinoxidativestressmediatedcelldeathofleukemiccells AT carameljulie e4f1deficiencyresultsinoxidativestressmediatedcelldeathofleukemiccells AT kirsholivier e4f1deficiencyresultsinoxidativestressmediatedcelldeathofleukemiccells AT jacquetchantal e4f1deficiencyresultsinoxidativestressmediatedcelldeathofleukemiccells AT schrepferemilie e4f1deficiencyresultsinoxidativestressmediatedcelldeathofleukemiccells AT lagarriguesylviane e4f1deficiencyresultsinoxidativestressmediatedcelldeathofleukemiccells AT linareslaetitiakarine e4f1deficiencyresultsinoxidativestressmediatedcelldeathofleukemiccells AT lledogwendaline e4f1deficiencyresultsinoxidativestressmediatedcelldeathofleukemiccells AT tondeursylvie e4f1deficiencyresultsinoxidativestressmediatedcelldeathofleukemiccells AT dubuspierre e4f1deficiencyresultsinoxidativestressmediatedcelldeathofleukemiccells AT sardetclaude e4f1deficiencyresultsinoxidativestressmediatedcelldeathofleukemiccells AT lecamlaurent e4f1deficiencyresultsinoxidativestressmediatedcelldeathofleukemiccells |