Study of PI3K/AKT/mTOR pathway in breast cancer progression

Autores
Novaro, Virginia
Año de publicación
2018
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Deregulation in the PI3K/AKT/mTOR pathway is associated with breast cancer development. Using experimental models of breast carcinogenesis induced in mice, xenografts of tumor cell lines, and tumors from patients we found a differential role of AKT1 and AKT2 isoforms in breast cancer progression. That is, AKT1 regulates nuclear proteins related to cell proliferation, such as cyclin D1 and pS6, whereas AKT2 regulates proteins related to cell migration and invasion such as vimentin, integrin b1, F-actin and FAK. Furthermore, activation of AKT1 promoted the hormone-independent and endocrine resistant phenotype, whereas activation of AKT2 lead to a more aggressive phenotype and lung metastasis. We analyzed 98 luminal breast carcinomas and found that nuclear AKT1 associates with low grade tumors, while cytosolic AKT2 associates with high grade tumors. Furthermore, presence of cytosolic AKT2 was positively correlated with a shorter time to progression of the disease (earlier relapse). In addition, based on our results and data analysis from public databases of The Cancer Genome Atlas, we postulate that throughout the progression of the disease there would be a switch between AKT1 and AKT2 isoforms, which maintains AKT2 inhibited while AKT1 prevails in the early stages. In the more advanced stages, this inhibition is lost and AKT2 prevails. Specific miRNAs are good candidates involved in this regulation and are now been tested in our lab in different experimental and clinical conditions. We propose the use of AKT1 and AKT2 isoforms determined by immunohistochemistry as prognostic markers that could help to better stratify breast tumors and direct more specific therapies.
Fil: Novaro, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
54 Annual Meeting Argentine Society for Biochemistry and Molcecular Biology: LIV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular
Parana
Argentina
Sociedad Argentina de Bioquímica
Consejo Nacional de Investigaciones Científicas y Técnicas
Fondo para la Investigación Científica y Tecnológica
Materia
BREAST CANCER
PROTEIN KINASE
TUMOR PROGRESSION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/131696
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Study of PI3K/AKT/mTOR pathway in breast cancer progressionNovaro, VirginiaBREAST CANCERPROTEIN KINASETUMOR PROGRESSIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Deregulation in the PI3K/AKT/mTOR pathway is associated with breast cancer development. Using experimental models of breast carcinogenesis induced in mice, xenografts of tumor cell lines, and tumors from patients we found a differential role of AKT1 and AKT2 isoforms in breast cancer progression. That is, AKT1 regulates nuclear proteins related to cell proliferation, such as cyclin D1 and pS6, whereas AKT2 regulates proteins related to cell migration and invasion such as vimentin, integrin b1, F-actin and FAK. Furthermore, activation of AKT1 promoted the hormone-independent and endocrine resistant phenotype, whereas activation of AKT2 lead to a more aggressive phenotype and lung metastasis. We analyzed 98 luminal breast carcinomas and found that nuclear AKT1 associates with low grade tumors, while cytosolic AKT2 associates with high grade tumors. Furthermore, presence of cytosolic AKT2 was positively correlated with a shorter time to progression of the disease (earlier relapse). In addition, based on our results and data analysis from public databases of The Cancer Genome Atlas, we postulate that throughout the progression of the disease there would be a switch between AKT1 and AKT2 isoforms, which maintains AKT2 inhibited while AKT1 prevails in the early stages. In the more advanced stages, this inhibition is lost and AKT2 prevails. Specific miRNAs are good candidates involved in this regulation and are now been tested in our lab in different experimental and clinical conditions. We propose the use of AKT1 and AKT2 isoforms determined by immunohistochemistry as prognostic markers that could help to better stratify breast tumors and direct more specific therapies.Fil: Novaro, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina54 Annual Meeting Argentine Society for Biochemistry and Molcecular Biology: LIV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología MolecularParanaArgentinaSociedad Argentina de BioquímicaConsejo Nacional de Investigaciones Científicas y TécnicasFondo para la Investigación Científica y TecnológicaInstituto de Histología y Embriología2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/131696Study of PI3K/AKT/mTOR pathway in breast cancer progression; 54 Annual Meeting Argentine Society for Biochemistry and Molcecular Biology: LIV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; Parana; Argentina; 2018; 151667-5746CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.saib.org.ar/sites/default/files/BIOCELL-SAIB-2018.pdfInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:39:33Zoai:ri.conicet.gov.ar:11336/131696instacron: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 10:39:33.26CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Study of PI3K/AKT/mTOR pathway in breast cancer progression
title Study of PI3K/AKT/mTOR pathway in breast cancer progression
spellingShingle Study of PI3K/AKT/mTOR pathway in breast cancer progression
Novaro, Virginia
BREAST CANCER
PROTEIN KINASE
TUMOR PROGRESSION
title_short Study of PI3K/AKT/mTOR pathway in breast cancer progression
title_full Study of PI3K/AKT/mTOR pathway in breast cancer progression
title_fullStr Study of PI3K/AKT/mTOR pathway in breast cancer progression
title_full_unstemmed Study of PI3K/AKT/mTOR pathway in breast cancer progression
title_sort Study of PI3K/AKT/mTOR pathway in breast cancer progression
dc.creator.none.fl_str_mv Novaro, Virginia
author Novaro, Virginia
author_facet Novaro, Virginia
author_role author
dc.subject.none.fl_str_mv BREAST CANCER
PROTEIN KINASE
TUMOR PROGRESSION
topic BREAST CANCER
PROTEIN KINASE
TUMOR PROGRESSION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Deregulation in the PI3K/AKT/mTOR pathway is associated with breast cancer development. Using experimental models of breast carcinogenesis induced in mice, xenografts of tumor cell lines, and tumors from patients we found a differential role of AKT1 and AKT2 isoforms in breast cancer progression. That is, AKT1 regulates nuclear proteins related to cell proliferation, such as cyclin D1 and pS6, whereas AKT2 regulates proteins related to cell migration and invasion such as vimentin, integrin b1, F-actin and FAK. Furthermore, activation of AKT1 promoted the hormone-independent and endocrine resistant phenotype, whereas activation of AKT2 lead to a more aggressive phenotype and lung metastasis. We analyzed 98 luminal breast carcinomas and found that nuclear AKT1 associates with low grade tumors, while cytosolic AKT2 associates with high grade tumors. Furthermore, presence of cytosolic AKT2 was positively correlated with a shorter time to progression of the disease (earlier relapse). In addition, based on our results and data analysis from public databases of The Cancer Genome Atlas, we postulate that throughout the progression of the disease there would be a switch between AKT1 and AKT2 isoforms, which maintains AKT2 inhibited while AKT1 prevails in the early stages. In the more advanced stages, this inhibition is lost and AKT2 prevails. Specific miRNAs are good candidates involved in this regulation and are now been tested in our lab in different experimental and clinical conditions. We propose the use of AKT1 and AKT2 isoforms determined by immunohistochemistry as prognostic markers that could help to better stratify breast tumors and direct more specific therapies.
Fil: Novaro, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
54 Annual Meeting Argentine Society for Biochemistry and Molcecular Biology: LIV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular
Parana
Argentina
Sociedad Argentina de Bioquímica
Consejo Nacional de Investigaciones Científicas y Técnicas
Fondo para la Investigación Científica y Tecnológica
description Deregulation in the PI3K/AKT/mTOR pathway is associated with breast cancer development. Using experimental models of breast carcinogenesis induced in mice, xenografts of tumor cell lines, and tumors from patients we found a differential role of AKT1 and AKT2 isoforms in breast cancer progression. That is, AKT1 regulates nuclear proteins related to cell proliferation, such as cyclin D1 and pS6, whereas AKT2 regulates proteins related to cell migration and invasion such as vimentin, integrin b1, F-actin and FAK. Furthermore, activation of AKT1 promoted the hormone-independent and endocrine resistant phenotype, whereas activation of AKT2 lead to a more aggressive phenotype and lung metastasis. We analyzed 98 luminal breast carcinomas and found that nuclear AKT1 associates with low grade tumors, while cytosolic AKT2 associates with high grade tumors. Furthermore, presence of cytosolic AKT2 was positively correlated with a shorter time to progression of the disease (earlier relapse). In addition, based on our results and data analysis from public databases of The Cancer Genome Atlas, we postulate that throughout the progression of the disease there would be a switch between AKT1 and AKT2 isoforms, which maintains AKT2 inhibited while AKT1 prevails in the early stages. In the more advanced stages, this inhibition is lost and AKT2 prevails. Specific miRNAs are good candidates involved in this regulation and are now been tested in our lab in different experimental and clinical conditions. We propose the use of AKT1 and AKT2 isoforms determined by immunohistochemistry as prognostic markers that could help to better stratify breast tumors and direct more specific therapies.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/131696
Study of PI3K/AKT/mTOR pathway in breast cancer progression; 54 Annual Meeting Argentine Society for Biochemistry and Molcecular Biology: LIV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; Parana; Argentina; 2018; 15
1667-5746
CONICET Digital
CONICET
url http://hdl.handle.net/11336/131696
identifier_str_mv Study of PI3K/AKT/mTOR pathway in breast cancer progression; 54 Annual Meeting Argentine Society for Biochemistry and Molcecular Biology: LIV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; Parana; Argentina; 2018; 15
1667-5746
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.saib.org.ar/sites/default/files/BIOCELL-SAIB-2018.pdf
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Instituto de Histología y Embriología
publisher.none.fl_str_mv Instituto de Histología y Embriología
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 13.070432

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