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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/15784
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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 Técnicas2025-09-29T09:51:49Zoai: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:34982025-09-29 09:51:49.588CONICET 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 |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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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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1844613592116101120 |
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13.070432 |