E2f1 and RB are common mediators of the inhibitory effects prompted by the combination of Mifepristone and Palbociclib on breast cancer cells expressing progesterone receptor Isofo...

Autores
Pataccini, Gabriela; Lanari, Claudia; Giulianelli, Sebastian Jesus
Año de publicación
2022
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Palbociclib (PALBO), a CDK 4/6 inhibitor, is currently used in combination with endocrine therapy targeting estrogen receptors to treat advanced luminal breast cancer. However, with time tumors become resistant to these treatments highlighting the need to develop other therapeutic strategies. Our laboratory focuses on the use of therapies targeting progesterone receptors (PR). We have previously shown that PALBO inhibits luminal breast cancer cell proliferation regardless of the prevailing PR isoform expressed and that mifepristone (MFP), an antiprogestin, potentiates this effect only in cells expressing PR isoform A (PRA). The aim of this study was to evaluate the role of two key cell cycle proteins, RB and E2F1 as mediators of this effect. T47D-YA or T47D-YB cells, expressing respectively PRA or PRB were treated with MFP, PALBO, or MFP+PALBO. The expression of E2F1 and pRB was evaluated by western blots. In agreement with data obtained in cell proliferation studies, a significant decrease of both protein levels (p<0.05) was observed only in T47D-YA cells treated with MFP+PALBO, whereas slight decreases were noted with single treatments. Contrarily, in T47D-YB cells, the effects of combined drugs were similar to those induced by PALBO. The in vivo growth of T47D cells expressing equimolar levels of PRA and PRB was also inhibited by the combined therapies and the strongest inhibition of pRB was registered by immunohistochemistry in tumors treated with both agents. Our results suggest that E2F1 and RB are key players mediating the inhibition of cell proliferation induced by PALBO and MFP combination exclusively in PRA-expressing cells. Mechanistic studies are underway to explore the direct involvement of PRA on the E2F1 promoter.
Fil: Pataccini, Gabriela. 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. 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: Giulianelli, Sebastian Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Biología de Organismos Marinos; Argentina. 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
Reunión Conjunta SAIC SAI & FAIC SAFIS 2022; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología; 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
Materia
PALBOCICLIB
BREAST CANCER
PROGESTERONE RECEPTOR
E2F RB
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:11336/250344
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling E2f1 and RB are common mediators of the inhibitory effects prompted by the combination of Mifepristone and Palbociclib on breast cancer cells expressing progesterone receptor Isoform APataccini, GabrielaLanari, ClaudiaGiulianelli, Sebastian JesusPALBOCICLIBBREAST CANCERPROGESTERONE RECEPTORE2F RBhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Palbociclib (PALBO), a CDK 4/6 inhibitor, is currently used in combination with endocrine therapy targeting estrogen receptors to treat advanced luminal breast cancer. However, with time tumors become resistant to these treatments highlighting the need to develop other therapeutic strategies. Our laboratory focuses on the use of therapies targeting progesterone receptors (PR). We have previously shown that PALBO inhibits luminal breast cancer cell proliferation regardless of the prevailing PR isoform expressed and that mifepristone (MFP), an antiprogestin, potentiates this effect only in cells expressing PR isoform A (PRA). The aim of this study was to evaluate the role of two key cell cycle proteins, RB and E2F1 as mediators of this effect. T47D-YA or T47D-YB cells, expressing respectively PRA or PRB were treated with MFP, PALBO, or MFP+PALBO. The expression of E2F1 and pRB was evaluated by western blots. In agreement with data obtained in cell proliferation studies, a significant decrease of both protein levels (p<0.05) was observed only in T47D-YA cells treated with MFP+PALBO, whereas slight decreases were noted with single treatments. Contrarily, in T47D-YB cells, the effects of combined drugs were similar to those induced by PALBO. The in vivo growth of T47D cells expressing equimolar levels of PRA and PRB was also inhibited by the combined therapies and the strongest inhibition of pRB was registered by immunohistochemistry in tumors treated with both agents. Our results suggest that E2F1 and RB are key players mediating the inhibition of cell proliferation induced by PALBO and MFP combination exclusively in PRA-expressing cells. Mechanistic studies are underway to explore the direct involvement of PRA on the E2F1 promoter.Fil: Pataccini, Gabriela. 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. 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: Giulianelli, Sebastian Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Biología de Organismos Marinos; Argentina. 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; ArgentinaReunión Conjunta SAIC SAI & FAIC SAFIS 2022; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología; 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de FisiologíaMar del PlataArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaSociedad Argentina de FisiologíaFundación Revista Medicina2022info: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/11336/250344E2f1 and RB are common mediators of the inhibitory effects prompted by the combination of Mifepristone and Palbociclib on breast cancer cells expressing progesterone receptor Isoform A; Reunión Conjunta SAIC SAI & FAIC SAFIS 2022; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología; 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2022; 249-2490025-7680CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/indices-de-2020/volumen-82-ano-2022-s5/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:43:37Zoai:ri.conicet.gov.ar:11336/250344instacron: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 09:43:37.536CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv E2f1 and RB are common mediators of the inhibitory effects prompted by the combination of Mifepristone and Palbociclib on breast cancer cells expressing progesterone receptor Isoform A
title E2f1 and RB are common mediators of the inhibitory effects prompted by the combination of Mifepristone and Palbociclib on breast cancer cells expressing progesterone receptor Isoform A
spellingShingle E2f1 and RB are common mediators of the inhibitory effects prompted by the combination of Mifepristone and Palbociclib on breast cancer cells expressing progesterone receptor Isoform A
Pataccini, Gabriela
PALBOCICLIB
BREAST CANCER
PROGESTERONE RECEPTOR
E2F RB
title_short E2f1 and RB are common mediators of the inhibitory effects prompted by the combination of Mifepristone and Palbociclib on breast cancer cells expressing progesterone receptor Isoform A
title_full E2f1 and RB are common mediators of the inhibitory effects prompted by the combination of Mifepristone and Palbociclib on breast cancer cells expressing progesterone receptor Isoform A
title_fullStr E2f1 and RB are common mediators of the inhibitory effects prompted by the combination of Mifepristone and Palbociclib on breast cancer cells expressing progesterone receptor Isoform A
title_full_unstemmed E2f1 and RB are common mediators of the inhibitory effects prompted by the combination of Mifepristone and Palbociclib on breast cancer cells expressing progesterone receptor Isoform A
title_sort E2f1 and RB are common mediators of the inhibitory effects prompted by the combination of Mifepristone and Palbociclib on breast cancer cells expressing progesterone receptor Isoform A
dc.creator.none.fl_str_mv Pataccini, Gabriela
Lanari, Claudia
Giulianelli, Sebastian Jesus
author Pataccini, Gabriela
author_facet Pataccini, Gabriela
Lanari, Claudia
Giulianelli, Sebastian Jesus
author_role author
author2 Lanari, Claudia
Giulianelli, Sebastian Jesus
author2_role author
author
dc.subject.none.fl_str_mv PALBOCICLIB
BREAST CANCER
PROGESTERONE RECEPTOR
E2F RB
topic PALBOCICLIB
BREAST CANCER
PROGESTERONE RECEPTOR
E2F RB
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Palbociclib (PALBO), a CDK 4/6 inhibitor, is currently used in combination with endocrine therapy targeting estrogen receptors to treat advanced luminal breast cancer. However, with time tumors become resistant to these treatments highlighting the need to develop other therapeutic strategies. Our laboratory focuses on the use of therapies targeting progesterone receptors (PR). We have previously shown that PALBO inhibits luminal breast cancer cell proliferation regardless of the prevailing PR isoform expressed and that mifepristone (MFP), an antiprogestin, potentiates this effect only in cells expressing PR isoform A (PRA). The aim of this study was to evaluate the role of two key cell cycle proteins, RB and E2F1 as mediators of this effect. T47D-YA or T47D-YB cells, expressing respectively PRA or PRB were treated with MFP, PALBO, or MFP+PALBO. The expression of E2F1 and pRB was evaluated by western blots. In agreement with data obtained in cell proliferation studies, a significant decrease of both protein levels (p<0.05) was observed only in T47D-YA cells treated with MFP+PALBO, whereas slight decreases were noted with single treatments. Contrarily, in T47D-YB cells, the effects of combined drugs were similar to those induced by PALBO. The in vivo growth of T47D cells expressing equimolar levels of PRA and PRB was also inhibited by the combined therapies and the strongest inhibition of pRB was registered by immunohistochemistry in tumors treated with both agents. Our results suggest that E2F1 and RB are key players mediating the inhibition of cell proliferation induced by PALBO and MFP combination exclusively in PRA-expressing cells. Mechanistic studies are underway to explore the direct involvement of PRA on the E2F1 promoter.
Fil: Pataccini, Gabriela. 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. 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: Giulianelli, Sebastian Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Biología de Organismos Marinos; Argentina. 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
Reunión Conjunta SAIC SAI & FAIC SAFIS 2022; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología; 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
description Palbociclib (PALBO), a CDK 4/6 inhibitor, is currently used in combination with endocrine therapy targeting estrogen receptors to treat advanced luminal breast cancer. However, with time tumors become resistant to these treatments highlighting the need to develop other therapeutic strategies. Our laboratory focuses on the use of therapies targeting progesterone receptors (PR). We have previously shown that PALBO inhibits luminal breast cancer cell proliferation regardless of the prevailing PR isoform expressed and that mifepristone (MFP), an antiprogestin, potentiates this effect only in cells expressing PR isoform A (PRA). The aim of this study was to evaluate the role of two key cell cycle proteins, RB and E2F1 as mediators of this effect. T47D-YA or T47D-YB cells, expressing respectively PRA or PRB were treated with MFP, PALBO, or MFP+PALBO. The expression of E2F1 and pRB was evaluated by western blots. In agreement with data obtained in cell proliferation studies, a significant decrease of both protein levels (p<0.05) was observed only in T47D-YA cells treated with MFP+PALBO, whereas slight decreases were noted with single treatments. Contrarily, in T47D-YB cells, the effects of combined drugs were similar to those induced by PALBO. The in vivo growth of T47D cells expressing equimolar levels of PRA and PRB was also inhibited by the combined therapies and the strongest inhibition of pRB was registered by immunohistochemistry in tumors treated with both agents. Our results suggest that E2F1 and RB are key players mediating the inhibition of cell proliferation induced by PALBO and MFP combination exclusively in PRA-expressing cells. Mechanistic studies are underway to explore the direct involvement of PRA on the E2F1 promoter.
publishDate 2022
dc.date.none.fl_str_mv 2022
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/11336/250344
E2f1 and RB are common mediators of the inhibitory effects prompted by the combination of Mifepristone and Palbociclib on breast cancer cells expressing progesterone receptor Isoform A; Reunión Conjunta SAIC SAI & FAIC SAFIS 2022; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología; 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2022; 249-249
0025-7680
CONICET Digital
CONICET
url http://hdl.handle.net/11336/250344
identifier_str_mv E2f1 and RB are common mediators of the inhibitory effects prompted by the combination of Mifepristone and Palbociclib on breast cancer cells expressing progesterone receptor Isoform A; Reunión Conjunta SAIC SAI & FAIC SAFIS 2022; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología; 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2022; 249-249
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/https://www.medicinabuenosaires.com/indices-de-2020/volumen-82-ano-2022-s5/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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