Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential

Autores
Vallone, Sabrina Aldana; Garcia Sola, Martin Emilio; Schere Levy, Carolina Paula; Meiss, Roberto P.; Hermida, Gladys Noemí; Chodosh, Lewis A.; Kordon, Edith Claudia; Hynes, Nancy E.; Gattelli, Albana
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
RET is a receptor tyrosine kinase with oncogenic potential in the mammary epithelium. Several receptors with oncogenic activity in the breast are known to participate in specific developmental stages. We found that RET is differentially expressed during mouse mammary gland development: RET is present in lactation and its expression dramatically decreases in involution, the period during which the lactating gland returns to a quiescent state after weaning. Based on epidemiological and pre-clinical findings, involution has been described as tumor promoting. Using the Ret/MTB doxycycline-inducible mouse transgenic system we show that sustained expression of RET in the mammary epithelium during the post-lactation transition to involution is accompanied by alterations in tissue remodeling and an enhancement of cancer potential. Following constitutive Ret expression we observed a significant increase in neoplastic lesions in the post-involuting versus the virgin mammary gland. Furthermore, we show that abnormal RET overexpression during lactation promotes factors that prime involution, including premature activation of Stat3 signaling and, using RNA-seq, an acute-phase inflammatory signature. Our results demonstrate that RET overexpression negatively affects the normal post-lactation transition.
Fil: Vallone, Sabrina Aldana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Garcia Sola, Martin Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Schere Levy, Carolina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Hermida, Gladys Noemí. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Chodosh, Lewis A.. University of Pennsylvania; Estados Unidos
Fil: Kordon, Edith Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Hynes, Nancy E.. Friedrich Miescher Institute For Biomedical Research; Suiza
Fil: Gattelli, Albana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Materia
RET
Mammary tumors
STAT
Involution
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:11336/214634
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/214634
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potentialVallone, Sabrina AldanaGarcia Sola, Martin EmilioSchere Levy, Carolina PaulaMeiss, Roberto P.Hermida, Gladys NoemíChodosh, Lewis A.Kordon, Edith ClaudiaHynes, Nancy E.Gattelli, AlbanaRETMammary tumorsSTATInvolutionhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3RET is a receptor tyrosine kinase with oncogenic potential in the mammary epithelium. Several receptors with oncogenic activity in the breast are known to participate in specific developmental stages. We found that RET is differentially expressed during mouse mammary gland development: RET is present in lactation and its expression dramatically decreases in involution, the period during which the lactating gland returns to a quiescent state after weaning. Based on epidemiological and pre-clinical findings, involution has been described as tumor promoting. Using the Ret/MTB doxycycline-inducible mouse transgenic system we show that sustained expression of RET in the mammary epithelium during the post-lactation transition to involution is accompanied by alterations in tissue remodeling and an enhancement of cancer potential. Following constitutive Ret expression we observed a significant increase in neoplastic lesions in the post-involuting versus the virgin mammary gland. Furthermore, we show that abnormal RET overexpression during lactation promotes factors that prime involution, including premature activation of Stat3 signaling and, using RNA-seq, an acute-phase inflammatory signature. Our results demonstrate that RET overexpression negatively affects the normal post-lactation transition.Fil: Vallone, Sabrina Aldana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Garcia Sola, Martin Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Schere Levy, Carolina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Hermida, Gladys Noemí. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Chodosh, Lewis A.. University of Pennsylvania; Estados UnidosFil: Kordon, Edith Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Hynes, Nancy E.. Friedrich Miescher Institute For Biomedical Research; SuizaFil: Gattelli, Albana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaCompany of Biologists2022-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/214634Vallone, Sabrina Aldana; Garcia Sola, Martin Emilio; Schere Levy, Carolina Paula; Meiss, Roberto P.; Hermida, Gladys Noemí; et al.; Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential; Company of Biologists; Disease Models And Mechanisms; 15; 3; 3-2022; 1-141754-84031754-8411CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.biologists.com/dmm/article/15/3/dmm049286/274874/Aberrant-RET-expression-affects-normal-mammaryinfo:eu-repo/semantics/altIdentifier/doi/10.1242/dmm.049286info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:51:22Zoai:ri.conicet.gov.ar:11336/214634instacron: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 09:51:22.311CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential
title Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential
spellingShingle Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential
Vallone, Sabrina Aldana
RET
Mammary tumors
STAT
Involution
title_short Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential
title_full Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential
title_fullStr Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential
title_full_unstemmed Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential
title_sort Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential
dc.creator.none.fl_str_mv Vallone, Sabrina Aldana
Garcia Sola, Martin Emilio
Schere Levy, Carolina Paula
Meiss, Roberto P.
Hermida, Gladys Noemí
Chodosh, Lewis A.
Kordon, Edith Claudia
Hynes, Nancy E.
Gattelli, Albana
author Vallone, Sabrina Aldana
author_facet Vallone, Sabrina Aldana
Garcia Sola, Martin Emilio
Schere Levy, Carolina Paula
Meiss, Roberto P.
Hermida, Gladys Noemí
Chodosh, Lewis A.
Kordon, Edith Claudia
Hynes, Nancy E.
Gattelli, Albana
author_role author
author2 Garcia Sola, Martin Emilio
Schere Levy, Carolina Paula
Meiss, Roberto P.
Hermida, Gladys Noemí
Chodosh, Lewis A.
Kordon, Edith Claudia
Hynes, Nancy E.
Gattelli, Albana
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv RET
Mammary tumors
STAT
Involution
topic RET
Mammary tumors
STAT
Involution
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv RET is a receptor tyrosine kinase with oncogenic potential in the mammary epithelium. Several receptors with oncogenic activity in the breast are known to participate in specific developmental stages. We found that RET is differentially expressed during mouse mammary gland development: RET is present in lactation and its expression dramatically decreases in involution, the period during which the lactating gland returns to a quiescent state after weaning. Based on epidemiological and pre-clinical findings, involution has been described as tumor promoting. Using the Ret/MTB doxycycline-inducible mouse transgenic system we show that sustained expression of RET in the mammary epithelium during the post-lactation transition to involution is accompanied by alterations in tissue remodeling and an enhancement of cancer potential. Following constitutive Ret expression we observed a significant increase in neoplastic lesions in the post-involuting versus the virgin mammary gland. Furthermore, we show that abnormal RET overexpression during lactation promotes factors that prime involution, including premature activation of Stat3 signaling and, using RNA-seq, an acute-phase inflammatory signature. Our results demonstrate that RET overexpression negatively affects the normal post-lactation transition.
Fil: Vallone, Sabrina Aldana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Garcia Sola, Martin Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Schere Levy, Carolina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Hermida, Gladys Noemí. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Chodosh, Lewis A.. University of Pennsylvania; Estados Unidos
Fil: Kordon, Edith Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Hynes, Nancy E.. Friedrich Miescher Institute For Biomedical Research; Suiza
Fil: Gattelli, Albana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
description RET is a receptor tyrosine kinase with oncogenic potential in the mammary epithelium. Several receptors with oncogenic activity in the breast are known to participate in specific developmental stages. We found that RET is differentially expressed during mouse mammary gland development: RET is present in lactation and its expression dramatically decreases in involution, the period during which the lactating gland returns to a quiescent state after weaning. Based on epidemiological and pre-clinical findings, involution has been described as tumor promoting. Using the Ret/MTB doxycycline-inducible mouse transgenic system we show that sustained expression of RET in the mammary epithelium during the post-lactation transition to involution is accompanied by alterations in tissue remodeling and an enhancement of cancer potential. Following constitutive Ret expression we observed a significant increase in neoplastic lesions in the post-involuting versus the virgin mammary gland. Furthermore, we show that abnormal RET overexpression during lactation promotes factors that prime involution, including premature activation of Stat3 signaling and, using RNA-seq, an acute-phase inflammatory signature. Our results demonstrate that RET overexpression negatively affects the normal post-lactation transition.
publishDate 2022
dc.date.none.fl_str_mv 2022-03
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/11336/214634
Vallone, Sabrina Aldana; Garcia Sola, Martin Emilio; Schere Levy, Carolina Paula; Meiss, Roberto P.; Hermida, Gladys Noemí; et al.; Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential; Company of Biologists; Disease Models And Mechanisms; 15; 3; 3-2022; 1-14
1754-8403
1754-8411
CONICET Digital
CONICET
url http://hdl.handle.net/11336/214634
identifier_str_mv Vallone, Sabrina Aldana; Garcia Sola, Martin Emilio; Schere Levy, Carolina Paula; Meiss, Roberto P.; Hermida, Gladys Noemí; et al.; Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential; Company of Biologists; Disease Models And Mechanisms; 15; 3; 3-2022; 1-14
1754-8403
1754-8411
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://journals.biologists.com/dmm/article/15/3/dmm049286/274874/Aberrant-RET-expression-affects-normal-mammary
info:eu-repo/semantics/altIdentifier/doi/10.1242/dmm.049286
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
application/pdf
dc.publisher.none.fl_str_mv Company of Biologists
publisher.none.fl_str_mv Company of Biologists
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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