Effect of Roscovitine and mifepristone on luminal breast cancer cell proliferation

Autores
Vottero, Lucía Andrea; Lanari, Claudia Lee Malvina; Fabris, Victoria Teresa
Año de publicación
2021
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The use of CDK2 inhibitors, such as Roscovitine (ROSCO),appears as a therapeutic alternative to overcome the acquisitionof resistance to Palbociclib in luminal breast cancer.The aim of this work was to evaluate the effect of ROSCOon cell proliferation in cells differing in their progesterone receptor(PR) isoform context. We have already demonstratedthat T47D-YB human breast cancer cells (only expressingisoform B; PRB) had increased cyclin A levels compared toT47D-YA cells (only expressing isoform A; PRA). We decidedto evaluate if cells overexpressing PRB would be moresensitive to CDK2 inhibitors than those overexpressing PRA.T47D, T47D-YA or T47D-YB cells were treated with FGF2to increase cell proliferation and then they were treated withROSCO 2 µM. All cells were similarly inhibited by ROSCO (p< 0.01) and this was accompanied by a decrease in the levelsof phospho-ERK. When FGF2-treated cells were incubatedwith ROSCO 1 µM and/or the antiprogestin mifepristone(MFP; 10 nM), only in T47D-YA cells the combined treatmentshowed significant inhibitory effects on cell proliferation thatwere stronger than those induced by the single treatments(p < 0.01). These results suggest that the levels of cyclin Aare not a biomarker of CDK2 inhibitor responsiveness. Inaddition, we show that CDK2 inhibitors may be an option forluminal breast cancer cells overexpressing PRA isoform incombination with antiprogestins.
Fil: Vottero, Lucía Andrea. 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
Fil: Lanari, Claudia Lee Malvina. 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
Fil: Fabris, Victoria Teresa. 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
Buenos Aires Breast Cancer Symposium
Buenos Aires
Argentina
Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”
Consejo Nacional de Investigaciones Científicas y Técnicas
Instituto de Biología y Medicina Experimental
Instituto de Fisiología, Biología Molecular y Neurociencias
Instituto de Investigaciones en Medicina Traslacional
Instituto de Nanosistemas
Universidad Austral
Universidad de Buenos Aires
Universidad Nacional de San Martín
Materia
BREAST CANCER
CDK2 INHIBITORS
PROGESTERONE RECEPTOR
CYCLIN A
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:11336/152879
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/152879
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Effect of Roscovitine and mifepristone on luminal breast cancer cell proliferationVottero, Lucía AndreaLanari, Claudia Lee MalvinaFabris, Victoria TeresaBREAST CANCERCDK2 INHIBITORSPROGESTERONE RECEPTORCYCLIN Ahttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The use of CDK2 inhibitors, such as Roscovitine (ROSCO),appears as a therapeutic alternative to overcome the acquisitionof resistance to Palbociclib in luminal breast cancer.The aim of this work was to evaluate the effect of ROSCOon cell proliferation in cells differing in their progesterone receptor(PR) isoform context. We have already demonstratedthat T47D-YB human breast cancer cells (only expressingisoform B; PRB) had increased cyclin A levels compared toT47D-YA cells (only expressing isoform A; PRA). We decidedto evaluate if cells overexpressing PRB would be moresensitive to CDK2 inhibitors than those overexpressing PRA.T47D, T47D-YA or T47D-YB cells were treated with FGF2to increase cell proliferation and then they were treated withROSCO 2 µM. All cells were similarly inhibited by ROSCO (p< 0.01) and this was accompanied by a decrease in the levelsof phospho-ERK. When FGF2-treated cells were incubatedwith ROSCO 1 µM and/or the antiprogestin mifepristone(MFP; 10 nM), only in T47D-YA cells the combined treatmentshowed significant inhibitory effects on cell proliferation thatwere stronger than those induced by the single treatments(p < 0.01). These results suggest that the levels of cyclin Aare not a biomarker of CDK2 inhibitor responsiveness. Inaddition, we show that CDK2 inhibitors may be an option forluminal breast cancer cells overexpressing PRA isoform incombination with antiprogestins.Fil: Vottero, Lucía Andrea. 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; ArgentinaFil: Lanari, Claudia Lee Malvina. 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; ArgentinaFil: Fabris, Victoria Teresa. 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; ArgentinaBuenos Aires Breast Cancer SymposiumBuenos AiresArgentinaCentro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”Consejo Nacional de Investigaciones Científicas y TécnicasInstituto de Biología y Medicina ExperimentalInstituto de Fisiología, Biología Molecular y NeurocienciasInstituto de Investigaciones en Medicina TraslacionalInstituto de NanosistemasUniversidad AustralUniversidad de Buenos AiresUniversidad Nacional de San MartínFundación Revista MedicinaKordon, Edith ClaudiaLanari, Claudia Lee MalvinaSimian, Marina2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectSimposioJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/152879Effect of Roscovitine and mifepristone on luminal breast cancer cell proliferation; Buenos Aires Breast Cancer Symposium; Buenos Aires; Argentina; 2021; 32-320025-7680CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S0025-76802021000600001&lng=es&nrm=iso&tlng=eninfo:eu-repo/semantics/altIdentifier/url/https://ba-bcs2020.com/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:35Zoai:ri.conicet.gov.ar:11336/152879instacron: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:34982025-09-03 09:51:35.915CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effect of Roscovitine and mifepristone on luminal breast cancer cell proliferation
title Effect of Roscovitine and mifepristone on luminal breast cancer cell proliferation
spellingShingle Effect of Roscovitine and mifepristone on luminal breast cancer cell proliferation
Vottero, Lucía Andrea
BREAST CANCER
CDK2 INHIBITORS
PROGESTERONE RECEPTOR
CYCLIN A
title_short Effect of Roscovitine and mifepristone on luminal breast cancer cell proliferation
title_full Effect of Roscovitine and mifepristone on luminal breast cancer cell proliferation
title_fullStr Effect of Roscovitine and mifepristone on luminal breast cancer cell proliferation
title_full_unstemmed Effect of Roscovitine and mifepristone on luminal breast cancer cell proliferation
title_sort Effect of Roscovitine and mifepristone on luminal breast cancer cell proliferation
dc.creator.none.fl_str_mv Vottero, Lucía Andrea
Lanari, Claudia Lee Malvina
Fabris, Victoria Teresa
author Vottero, Lucía Andrea
author_facet Vottero, Lucía Andrea
Lanari, Claudia Lee Malvina
Fabris, Victoria Teresa
author_role author
author2 Lanari, Claudia Lee Malvina
Fabris, Victoria Teresa
author2_role author
author
dc.contributor.none.fl_str_mv Kordon, Edith Claudia
Lanari, Claudia Lee Malvina
Simian, Marina
dc.subject.none.fl_str_mv BREAST CANCER
CDK2 INHIBITORS
PROGESTERONE RECEPTOR
CYCLIN A
topic BREAST CANCER
CDK2 INHIBITORS
PROGESTERONE RECEPTOR
CYCLIN A
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The use of CDK2 inhibitors, such as Roscovitine (ROSCO),appears as a therapeutic alternative to overcome the acquisitionof resistance to Palbociclib in luminal breast cancer.The aim of this work was to evaluate the effect of ROSCOon cell proliferation in cells differing in their progesterone receptor(PR) isoform context. We have already demonstratedthat T47D-YB human breast cancer cells (only expressingisoform B; PRB) had increased cyclin A levels compared toT47D-YA cells (only expressing isoform A; PRA). We decidedto evaluate if cells overexpressing PRB would be moresensitive to CDK2 inhibitors than those overexpressing PRA.T47D, T47D-YA or T47D-YB cells were treated with FGF2to increase cell proliferation and then they were treated withROSCO 2 µM. All cells were similarly inhibited by ROSCO (p< 0.01) and this was accompanied by a decrease in the levelsof phospho-ERK. When FGF2-treated cells were incubatedwith ROSCO 1 µM and/or the antiprogestin mifepristone(MFP; 10 nM), only in T47D-YA cells the combined treatmentshowed significant inhibitory effects on cell proliferation thatwere stronger than those induced by the single treatments(p < 0.01). These results suggest that the levels of cyclin Aare not a biomarker of CDK2 inhibitor responsiveness. Inaddition, we show that CDK2 inhibitors may be an option forluminal breast cancer cells overexpressing PRA isoform incombination with antiprogestins.
Fil: Vottero, Lucía Andrea. 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
Fil: Lanari, Claudia Lee Malvina. 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
Fil: Fabris, Victoria Teresa. 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
Buenos Aires Breast Cancer Symposium
Buenos Aires
Argentina
Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”
Consejo Nacional de Investigaciones Científicas y Técnicas
Instituto de Biología y Medicina Experimental
Instituto de Fisiología, Biología Molecular y Neurociencias
Instituto de Investigaciones en Medicina Traslacional
Instituto de Nanosistemas
Universidad Austral
Universidad de Buenos Aires
Universidad Nacional de San Martín
description The use of CDK2 inhibitors, such as Roscovitine (ROSCO),appears as a therapeutic alternative to overcome the acquisitionof resistance to Palbociclib in luminal breast cancer.The aim of this work was to evaluate the effect of ROSCOon cell proliferation in cells differing in their progesterone receptor(PR) isoform context. We have already demonstratedthat T47D-YB human breast cancer cells (only expressingisoform B; PRB) had increased cyclin A levels compared toT47D-YA cells (only expressing isoform A; PRA). We decidedto evaluate if cells overexpressing PRB would be moresensitive to CDK2 inhibitors than those overexpressing PRA.T47D, T47D-YA or T47D-YB cells were treated with FGF2to increase cell proliferation and then they were treated withROSCO 2 µM. All cells were similarly inhibited by ROSCO (p< 0.01) and this was accompanied by a decrease in the levelsof phospho-ERK. When FGF2-treated cells were incubatedwith ROSCO 1 µM and/or the antiprogestin mifepristone(MFP; 10 nM), only in T47D-YA cells the combined treatmentshowed significant inhibitory effects on cell proliferation thatwere stronger than those induced by the single treatments(p < 0.01). These results suggest that the levels of cyclin Aare not a biomarker of CDK2 inhibitor responsiveness. Inaddition, we show that CDK2 inhibitors may be an option forluminal breast cancer cells overexpressing PRA isoform incombination with antiprogestins.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Simposio
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/11336/152879
Effect of Roscovitine and mifepristone on luminal breast cancer cell proliferation; Buenos Aires Breast Cancer Symposium; Buenos Aires; Argentina; 2021; 32-32
0025-7680
CONICET Digital
CONICET
url http://hdl.handle.net/11336/152879
identifier_str_mv Effect of Roscovitine and mifepristone on luminal breast cancer cell proliferation; Buenos Aires Breast Cancer Symposium; Buenos Aires; Argentina; 2021; 32-32
0025-7680
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.scielo.org.ar/scielo.php?script=sci_arttext&pid=S0025-76802021000600001&lng=es&nrm=iso&tlng=en
info:eu-repo/semantics/altIdentifier/url/https://ba-bcs2020.com/
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 Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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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