Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus

The PIM family of Ser/Thr kinase proteins has been implicated in tumorigenesis at different levels. PIM proteins are overexpressed in several tumor types and have been associated with chemoresistance. However, their role in hormone-dependent female tissues has not been explored, especially in the ut...

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Autores: Jiménez-García, Manuel-Pedro, Lucena-Cacace, Antonio, Robles-Frías, María-José, Ferrer, Irene, Narlik-Grassow, Maja, Blanco-Aparicio, Carmen, Carnero, Amancio
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/7335
Acceso en línea:http://hdl.handle.net/20.500.12105/7335
Access Level:acceso abierto
Palabra clave:Prostate
CHRONIC LYMPHOCYTIC-LEUKEMIA
PIM KINASES
SERINE/THREONINE KINASES
PANCREATIC-CANCER
Up-Regulation
Survival
Growth
Family
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network_acronym_str ES
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repository_id_str
spelling Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterusJiménez-García, Manuel-PedroLucena-Cacace, AntonioRobles-Frías, María-JoséFerrer, IreneNarlik-Grassow, MajaBlanco-Aparicio, CarmenCarnero, AmancioProstateCHRONIC LYMPHOCYTIC-LEUKEMIAPIM KINASESSERINE/THREONINE KINASESPANCREATIC-CANCERUp-RegulationSurvivalGrowthFamilyThe PIM family of Ser/Thr kinase proteins has been implicated in tumorigenesis at different levels. PIM proteins are overexpressed in several tumor types and have been associated with chemoresistance. However, their role in hormone-dependent female tissues has not been explored, especially in the uterus, breast and ovary. We generated conditional transgenic mice with confined expression of human PIM1 or PIM2 genes in these tissues. We characterized the tumoral response to these genetic alterations corroborating their role as oncogenes since they induce hyperproliferation in all tissues and tumors in mammary gland and uterus. Furthermore, we observed a high degree of inflammatory infiltration in these tissues of transgenic mice accompanied by NFAT and mTOR activation and IL6 expression. Moreover, PIM1/2 were overexpressed in human breast, uterine and ovarian tumors, correlating with inflammatory features and stem cell markers. Our data suggest that PIM1/2 kinase overexpression provoke tissue alterations and a large IL6-dependent inflammatory response that may act synergistically during the process of tumorigenesis. The possible end-point is an increased percentage of cancer stem cells, which may be partly responsible for the therapy resistance found in tumors overexpressing PIM kinases.Impact JournalsMinisterio de Economía y Competitividad (España)Centro de Investigación Biomedica en Red - CIBERUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Regional Government of Andalusia (España)Asociación Española Contra el Cáncer20192019-03-1420172017-08-2920172017-08-29journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documenthttp://hdl.handle.net/20.500.12105/7335reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES PI15 00045ES CD16 12ES CTS-1848 Not availableES PI-0096-2014 Not availableES FPU13 00426open accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/73352026-06-12T12:43:37Z
dc.title.none.fl_str_mv Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus
title Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus
spellingShingle Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus
Jiménez-García, Manuel-Pedro
Prostate
CHRONIC LYMPHOCYTIC-LEUKEMIA
PIM KINASES
SERINE/THREONINE KINASES
PANCREATIC-CANCER
Up-Regulation
Survival
Growth
Family
title_short Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus
title_full Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus
title_fullStr Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus
title_full_unstemmed Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus
title_sort Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus
dc.creator.none.fl_str_mv Jiménez-García, Manuel-Pedro
Lucena-Cacace, Antonio
Robles-Frías, María-José
Ferrer, Irene
Narlik-Grassow, Maja
Blanco-Aparicio, Carmen
Carnero, Amancio
author Jiménez-García, Manuel-Pedro
author_facet Jiménez-García, Manuel-Pedro
Lucena-Cacace, Antonio
Robles-Frías, María-José
Ferrer, Irene
Narlik-Grassow, Maja
Blanco-Aparicio, Carmen
Carnero, Amancio
author_role author
author2 Lucena-Cacace, Antonio
Robles-Frías, María-José
Ferrer, Irene
Narlik-Grassow, Maja
Blanco-Aparicio, Carmen
Carnero, Amancio
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Centro de Investigación Biomedica en Red - CIBER
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Regional Government of Andalusia (España)
Asociación Española Contra el Cáncer
dc.subject.none.fl_str_mv Prostate
CHRONIC LYMPHOCYTIC-LEUKEMIA
PIM KINASES
SERINE/THREONINE KINASES
PANCREATIC-CANCER
Up-Regulation
Survival
Growth
Family
topic Prostate
CHRONIC LYMPHOCYTIC-LEUKEMIA
PIM KINASES
SERINE/THREONINE KINASES
PANCREATIC-CANCER
Up-Regulation
Survival
Growth
Family
description The PIM family of Ser/Thr kinase proteins has been implicated in tumorigenesis at different levels. PIM proteins are overexpressed in several tumor types and have been associated with chemoresistance. However, their role in hormone-dependent female tissues has not been explored, especially in the uterus, breast and ovary. We generated conditional transgenic mice with confined expression of human PIM1 or PIM2 genes in these tissues. We characterized the tumoral response to these genetic alterations corroborating their role as oncogenes since they induce hyperproliferation in all tissues and tumors in mammary gland and uterus. Furthermore, we observed a high degree of inflammatory infiltration in these tissues of transgenic mice accompanied by NFAT and mTOR activation and IL6 expression. Moreover, PIM1/2 were overexpressed in human breast, uterine and ovarian tumors, correlating with inflammatory features and stem cell markers. Our data suggest that PIM1/2 kinase overexpression provoke tissue alterations and a large IL6-dependent inflammatory response that may act synergistically during the process of tumorigenesis. The possible end-point is an increased percentage of cancer stem cells, which may be partly responsible for the therapy resistance found in tumors overexpressing PIM kinases.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-08-29
2017
2017-08-29
2019
2019-03-14
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/7335
url http://hdl.handle.net/20.500.12105/7335
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv ES PI15 00045
ES CD16 12
ES CTS-1848 Not available
ES PI-0096-2014 Not available
ES FPU13 00426
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
application/vnd.openxmlformats-officedocument.wordprocessingml.document
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869411450876854272
score 15,81155

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