Reduced malignancy as a mechanism for longevity in mice with adenylyl cyclase type 5 disruption

Autores
De Lorenzo, Mariana S.; Chen, Wen; Baljinnyam, Erdene; Carlini, María José; La Perle, Krista; Bishop, Sanford P.; Wagner, Thomas E.; Rabson, Arnold B.; Vatner, Dorothy E.; Puricelli, Lydia Ines; Vatner, Stephen F.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Disruption of adenylyl cyclase type 5 (AC5) knockout (KO) is a novel model for longevity. Because malignancy is a major cause of death and reduced lifespan in mice, the goal of this investigation was to examine the role of AC5KO in protecting against cancer. There have been numerous discoveries in genetically engineered mice over the past several decades, but few have been translated to the bedside. One major reason is that it is difficult to alter a gene in patients, but rather a pharmacological approach is more appropriate. The current investigation employs a parallel construction to examine the extent to which inhibiting AC5, either in a genetic knockout (KO) or by a specific pharmacological inhibitor protects against cancer. This study is unique, not only because a combined genetic and pharmacological approach is rare, but also there are no prior studies on the extent to which AC5 affects cancer. We found that AC5KO delayed age-related tumor incidence significantly, as well as protecting against mammary tumor development in AC5KO × MMTV-HER-2 neu mice, and B16F10 melanoma tumor growth, which can explain why AC5KO is a model of longevity. In addition, a Food and Drug Administration approved antiviral agent, adenine 9-β-D-arabinofuranoside (Vidarabine or AraAde), which specifically inhibits AC5, reduces LP07 lung and B16F10 melanoma tumor growth in syngeneic mice. Thus, inhibition of AC5 is a previously unreported mechanism for prevention of cancers associated with aging and that can be targeted by an available pharmacologic inhibitor, with potential consequent extension of lifespan.
Fil: De Lorenzo, Mariana S.. State University of New Jersey; Estados Unidos
Fil: Chen, Wen. Clemson University; Estados Unidos
Fil: Baljinnyam, Erdene. State University of New Jersey; Estados Unidos
Fil: Carlini, María José. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: La Perle, Krista. Ohio State University; Estados Unidos
Fil: Bishop, Sanford P.. State University of New Jersey; Estados Unidos
Fil: Wagner, Thomas E.. Clemson University; Estados Unidos
Fil: Rabson, Arnold B.. State University of New Jersey; Estados Unidos
Fil: Vatner, Dorothy E.. State University of New Jersey; Estados Unidos
Fil: Puricelli, Lydia Ines. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Vatner, Stephen F.. State University of New Jersey; Estados Unidos
Materia
Adenylyl cyclase
Metabolism
Obesity
Tumor protection
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/15784
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/15784
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Reduced malignancy as a mechanism for longevity in mice with adenylyl cyclase type 5 disruptionDe Lorenzo, Mariana S.Chen, WenBaljinnyam, ErdeneCarlini, María JoséLa Perle, KristaBishop, Sanford P.Wagner, Thomas E.Rabson, Arnold B.Vatner, Dorothy E.Puricelli, Lydia InesVatner, Stephen F.Adenylyl cyclaseMetabolismObesityTumor protectionhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Disruption of adenylyl cyclase type 5 (AC5) knockout (KO) is a novel model for longevity. Because malignancy is a major cause of death and reduced lifespan in mice, the goal of this investigation was to examine the role of AC5KO in protecting against cancer. There have been numerous discoveries in genetically engineered mice over the past several decades, but few have been translated to the bedside. One major reason is that it is difficult to alter a gene in patients, but rather a pharmacological approach is more appropriate. The current investigation employs a parallel construction to examine the extent to which inhibiting AC5, either in a genetic knockout (KO) or by a specific pharmacological inhibitor protects against cancer. This study is unique, not only because a combined genetic and pharmacological approach is rare, but also there are no prior studies on the extent to which AC5 affects cancer. We found that AC5KO delayed age-related tumor incidence significantly, as well as protecting against mammary tumor development in AC5KO × MMTV-HER-2 neu mice, and B16F10 melanoma tumor growth, which can explain why AC5KO is a model of longevity. In addition, a Food and Drug Administration approved antiviral agent, adenine 9-β-D-arabinofuranoside (Vidarabine or AraAde), which specifically inhibits AC5, reduces LP07 lung and B16F10 melanoma tumor growth in syngeneic mice. Thus, inhibition of AC5 is a previously unreported mechanism for prevention of cancers associated with aging and that can be targeted by an available pharmacologic inhibitor, with potential consequent extension of lifespan.Fil: De Lorenzo, Mariana S.. State University of New Jersey; Estados UnidosFil: Chen, Wen. Clemson University; Estados UnidosFil: Baljinnyam, Erdene. State University of New Jersey; Estados UnidosFil: Carlini, María José. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: La Perle, Krista. Ohio State University; Estados UnidosFil: Bishop, Sanford P.. State University of New Jersey; Estados UnidosFil: Wagner, Thomas E.. Clemson University; Estados UnidosFil: Rabson, Arnold B.. State University of New Jersey; Estados UnidosFil: Vatner, Dorothy E.. State University of New Jersey; Estados UnidosFil: Puricelli, Lydia Ines. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vatner, Stephen F.. State University of New Jersey; Estados UnidosWiley2014-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/15784De Lorenzo, Mariana S.; Chen, Wen; Baljinnyam, Erdene; Carlini, María José; La Perle, Krista; et al.; Reduced malignancy as a mechanism for longevity in mice with adenylyl cyclase type 5 disruption; Wiley; Aging Cell; 13; 1; 2-2014; 102-1101474-9718enginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/acel.12152/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1111/acel.12152info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980454/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:46:32Zoai:ri.conicet.gov.ar:11336/15784instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:46:33.103CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Reduced malignancy as a mechanism for longevity in mice with adenylyl cyclase type 5 disruption
title Reduced malignancy as a mechanism for longevity in mice with adenylyl cyclase type 5 disruption
spellingShingle Reduced malignancy as a mechanism for longevity in mice with adenylyl cyclase type 5 disruption
De Lorenzo, Mariana S.
Adenylyl cyclase
Metabolism
Obesity
Tumor protection
title_short Reduced malignancy as a mechanism for longevity in mice with adenylyl cyclase type 5 disruption
title_full Reduced malignancy as a mechanism for longevity in mice with adenylyl cyclase type 5 disruption
title_fullStr Reduced malignancy as a mechanism for longevity in mice with adenylyl cyclase type 5 disruption
title_full_unstemmed Reduced malignancy as a mechanism for longevity in mice with adenylyl cyclase type 5 disruption
title_sort Reduced malignancy as a mechanism for longevity in mice with adenylyl cyclase type 5 disruption
dc.creator.none.fl_str_mv De Lorenzo, Mariana S.
Chen, Wen
Baljinnyam, Erdene
Carlini, María José
La Perle, Krista
Bishop, Sanford P.
Wagner, Thomas E.
Rabson, Arnold B.
Vatner, Dorothy E.
Puricelli, Lydia Ines
Vatner, Stephen F.
author De Lorenzo, Mariana S.
author_facet De Lorenzo, Mariana S.
Chen, Wen
Baljinnyam, Erdene
Carlini, María José
La Perle, Krista
Bishop, Sanford P.
Wagner, Thomas E.
Rabson, Arnold B.
Vatner, Dorothy E.
Puricelli, Lydia Ines
Vatner, Stephen F.
author_role author
author2 Chen, Wen
Baljinnyam, Erdene
Carlini, María José
La Perle, Krista
Bishop, Sanford P.
Wagner, Thomas E.
Rabson, Arnold B.
Vatner, Dorothy E.
Puricelli, Lydia Ines
Vatner, Stephen F.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Adenylyl cyclase
Metabolism
Obesity
Tumor protection
topic Adenylyl cyclase
Metabolism
Obesity
Tumor protection
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Disruption of adenylyl cyclase type 5 (AC5) knockout (KO) is a novel model for longevity. Because malignancy is a major cause of death and reduced lifespan in mice, the goal of this investigation was to examine the role of AC5KO in protecting against cancer. There have been numerous discoveries in genetically engineered mice over the past several decades, but few have been translated to the bedside. One major reason is that it is difficult to alter a gene in patients, but rather a pharmacological approach is more appropriate. The current investigation employs a parallel construction to examine the extent to which inhibiting AC5, either in a genetic knockout (KO) or by a specific pharmacological inhibitor protects against cancer. This study is unique, not only because a combined genetic and pharmacological approach is rare, but also there are no prior studies on the extent to which AC5 affects cancer. We found that AC5KO delayed age-related tumor incidence significantly, as well as protecting against mammary tumor development in AC5KO × MMTV-HER-2 neu mice, and B16F10 melanoma tumor growth, which can explain why AC5KO is a model of longevity. In addition, a Food and Drug Administration approved antiviral agent, adenine 9-β-D-arabinofuranoside (Vidarabine or AraAde), which specifically inhibits AC5, reduces LP07 lung and B16F10 melanoma tumor growth in syngeneic mice. Thus, inhibition of AC5 is a previously unreported mechanism for prevention of cancers associated with aging and that can be targeted by an available pharmacologic inhibitor, with potential consequent extension of lifespan.
Fil: De Lorenzo, Mariana S.. State University of New Jersey; Estados Unidos
Fil: Chen, Wen. Clemson University; Estados Unidos
Fil: Baljinnyam, Erdene. State University of New Jersey; Estados Unidos
Fil: Carlini, María José. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: La Perle, Krista. Ohio State University; Estados Unidos
Fil: Bishop, Sanford P.. State University of New Jersey; Estados Unidos
Fil: Wagner, Thomas E.. Clemson University; Estados Unidos
Fil: Rabson, Arnold B.. State University of New Jersey; Estados Unidos
Fil: Vatner, Dorothy E.. State University of New Jersey; Estados Unidos
Fil: Puricelli, Lydia Ines. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Vatner, Stephen F.. State University of New Jersey; Estados Unidos
description Disruption of adenylyl cyclase type 5 (AC5) knockout (KO) is a novel model for longevity. Because malignancy is a major cause of death and reduced lifespan in mice, the goal of this investigation was to examine the role of AC5KO in protecting against cancer. There have been numerous discoveries in genetically engineered mice over the past several decades, but few have been translated to the bedside. One major reason is that it is difficult to alter a gene in patients, but rather a pharmacological approach is more appropriate. The current investigation employs a parallel construction to examine the extent to which inhibiting AC5, either in a genetic knockout (KO) or by a specific pharmacological inhibitor protects against cancer. This study is unique, not only because a combined genetic and pharmacological approach is rare, but also there are no prior studies on the extent to which AC5 affects cancer. We found that AC5KO delayed age-related tumor incidence significantly, as well as protecting against mammary tumor development in AC5KO × MMTV-HER-2 neu mice, and B16F10 melanoma tumor growth, which can explain why AC5KO is a model of longevity. In addition, a Food and Drug Administration approved antiviral agent, adenine 9-β-D-arabinofuranoside (Vidarabine or AraAde), which specifically inhibits AC5, reduces LP07 lung and B16F10 melanoma tumor growth in syngeneic mice. Thus, inhibition of AC5 is a previously unreported mechanism for prevention of cancers associated with aging and that can be targeted by an available pharmacologic inhibitor, with potential consequent extension of lifespan.
publishDate 2014
dc.date.none.fl_str_mv 2014-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/15784
De Lorenzo, Mariana S.; Chen, Wen; Baljinnyam, Erdene; Carlini, María José; La Perle, Krista; et al.; Reduced malignancy as a mechanism for longevity in mice with adenylyl cyclase type 5 disruption; Wiley; Aging Cell; 13; 1; 2-2014; 102-110
1474-9718
url http://hdl.handle.net/11336/15784
identifier_str_mv De Lorenzo, Mariana S.; Chen, Wen; Baljinnyam, Erdene; Carlini, María José; La Perle, Krista; et al.; Reduced malignancy as a mechanism for longevity in mice with adenylyl cyclase type 5 disruption; Wiley; Aging Cell; 13; 1; 2-2014; 102-110
1474-9718
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/acel.12152/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1111/acel.12152
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980454/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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