R-RAS2 overexpression in tumors of the human central nervous system

Malignant tumors of the central nervous system (CNS) are the 10th most frequent cause of cancer mortality. Despite the strong malignancy of some such tumors, oncogenic mutations are rarely found in classic members of the RAS family of small GTPases. This raises the question as to whether other RAS f...

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Autores: Gutiérrez-Erlandsson, Sylvia, Herrero-Vidal, Pedro, Fernández-Alfara, Marcos, Hernández-García, Susana, Gonzalo-Flores, Sandra, Mudarra-Rubio, Alberto, Fresno Escudero, Manuel, Cubelos Álvarez, Beatriz
Tipo de recurso: artículo
Fecha de publicación:2013
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/660661
Acceso en línea:http://hdl.handle.net/10486/660661
https://dx.doi.org/10.1186/1476-4598-12-127
Access Level:acceso abierto
Palabra clave:RAS family proteins
R-RAS2
CNS tumors
TC21
Biología y Biomedicina / Biología
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spelling R-RAS2 overexpression in tumors of the human central nervous systemGutiérrez-Erlandsson, SylviaHerrero-Vidal, PedroFernández-Alfara, MarcosHernández-García, SusanaGonzalo-Flores, SandraMudarra-Rubio, AlbertoFresno Escudero, ManuelCubelos Álvarez, BeatrizRAS family proteinsR-RAS2CNS tumorsTC21Biología y Biomedicina / BiologíaMalignant tumors of the central nervous system (CNS) are the 10th most frequent cause of cancer mortality. Despite the strong malignancy of some such tumors, oncogenic mutations are rarely found in classic members of the RAS family of small GTPases. This raises the question as to whether other RAS family members may be affected in CNS tumors, excessively activating RAS pathways. The RAS-related subfamily of GTPases is that which is most closely related to classical Ras and it currently contains 3 members: RRAS, RRAS2 and RRAS3. While R-RAS and R-RAS2 are expressed ubiquitously, R-RAS3 expression is restricted to the CNS. Significantly, both wild type and mutated RRAS2 (also known as TC21) are overexpressed in human carcinomas of the oral cavity, esophagus, stomach, skin and breast, as well as in lymphomas. Hence, we analyzed the expression of R-RAS2 mRNA and protein in a wide variety of human CNS tumors and we found the R-RAS2 protein to be overexpressed in all of the 90 CNS cancer samples studied, including glioblastomas, astrocytomas and oligodendrogliomas. However, R-Ras2 was more strongly expressed in low grade (World Health Organization grades I-II) rather than high grade (grades III-IV) tumors, suggesting that R-RAS2 is overexpressed in the early stages of malignancy. Indeed, R-RAS2 overexpression was evident in pre-malignant hyperplasias, both at the mRNA and protein levels. Nevertheless, such dramatic changes in expression were not evident for the other two subfamily members, which implies that RRAS2 is the main factor triggering neural transformation.This work was supported by grants SAF2012-31279 from the ‘Comisión Interministerial de Ciencia y Tecnología’ and the ‘Ramón y Cajal’ program (RYC-2010-06251, to B.C.). We also thank the Fundación Ramón Areces for its institutional support of the ‘Centro de Biología Molecular Severo Ochoa’.BioMed CentralDepartamento de Biología MolecularFacultad de Ciencias20132013-10-23research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/660661https://dx.doi.org/10.1186/1476-4598-12-127reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6606612026-06-23T12:46:27Z
dc.title.none.fl_str_mv R-RAS2 overexpression in tumors of the human central nervous system
title R-RAS2 overexpression in tumors of the human central nervous system
spellingShingle R-RAS2 overexpression in tumors of the human central nervous system
Gutiérrez-Erlandsson, Sylvia
RAS family proteins
R-RAS2
CNS tumors
TC21
Biología y Biomedicina / Biología
title_short R-RAS2 overexpression in tumors of the human central nervous system
title_full R-RAS2 overexpression in tumors of the human central nervous system
title_fullStr R-RAS2 overexpression in tumors of the human central nervous system
title_full_unstemmed R-RAS2 overexpression in tumors of the human central nervous system
title_sort R-RAS2 overexpression in tumors of the human central nervous system
dc.creator.none.fl_str_mv Gutiérrez-Erlandsson, Sylvia
Herrero-Vidal, Pedro
Fernández-Alfara, Marcos
Hernández-García, Susana
Gonzalo-Flores, Sandra
Mudarra-Rubio, Alberto
Fresno Escudero, Manuel
Cubelos Álvarez, Beatriz
author Gutiérrez-Erlandsson, Sylvia
author_facet Gutiérrez-Erlandsson, Sylvia
Herrero-Vidal, Pedro
Fernández-Alfara, Marcos
Hernández-García, Susana
Gonzalo-Flores, Sandra
Mudarra-Rubio, Alberto
Fresno Escudero, Manuel
Cubelos Álvarez, Beatriz
author_role author
author2 Herrero-Vidal, Pedro
Fernández-Alfara, Marcos
Hernández-García, Susana
Gonzalo-Flores, Sandra
Mudarra-Rubio, Alberto
Fresno Escudero, Manuel
Cubelos Álvarez, Beatriz
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv RAS family proteins
R-RAS2
CNS tumors
TC21
Biología y Biomedicina / Biología
topic RAS family proteins
R-RAS2
CNS tumors
TC21
Biología y Biomedicina / Biología
description Malignant tumors of the central nervous system (CNS) are the 10th most frequent cause of cancer mortality. Despite the strong malignancy of some such tumors, oncogenic mutations are rarely found in classic members of the RAS family of small GTPases. This raises the question as to whether other RAS family members may be affected in CNS tumors, excessively activating RAS pathways. The RAS-related subfamily of GTPases is that which is most closely related to classical Ras and it currently contains 3 members: RRAS, RRAS2 and RRAS3. While R-RAS and R-RAS2 are expressed ubiquitously, R-RAS3 expression is restricted to the CNS. Significantly, both wild type and mutated RRAS2 (also known as TC21) are overexpressed in human carcinomas of the oral cavity, esophagus, stomach, skin and breast, as well as in lymphomas. Hence, we analyzed the expression of R-RAS2 mRNA and protein in a wide variety of human CNS tumors and we found the R-RAS2 protein to be overexpressed in all of the 90 CNS cancer samples studied, including glioblastomas, astrocytomas and oligodendrogliomas. However, R-Ras2 was more strongly expressed in low grade (World Health Organization grades I-II) rather than high grade (grades III-IV) tumors, suggesting that R-RAS2 is overexpressed in the early stages of malignancy. Indeed, R-RAS2 overexpression was evident in pre-malignant hyperplasias, both at the mRNA and protein levels. Nevertheless, such dramatic changes in expression were not evident for the other two subfamily members, which implies that RRAS2 is the main factor triggering neural transformation.
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-10-23
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
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/10486/660661
https://dx.doi.org/10.1186/1476-4598-12-127
url http://hdl.handle.net/10486/660661
https://dx.doi.org/10.1186/1476-4598-12-127
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
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
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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