Fulvestrant treatment alters MDM2 protein turnover and sensitivity of human breast carcinoma cells to chemotherapeutic drugs

Autores
Dolfi, Sonia C.; Jager, Adriana Valeria; Medina, Daniel J.; Haffty, Bruce G.; Yang, Jin Ming; Hirshfield, Kim M.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The human homologue of mouse double minute 2 (MDM2) is overexpressed in tumors and contributes to tumorigenesis through inhibition of p53 activity. We investigated the effect of the anti-estrogen fulvestrant on MDM2 expression and sensitivity of estrogen receptor positive human breast cancer cell lines to chemotherapeutics. Fulvestrant down-regulated MDM2 through increased protein turnover. Fulvestrant blocked estrogen-dependent up-regulation of MDM2 and decreased basal expression of MDM2 in the absence of estradiol. As combinations of fulvestrant with doxorubicin, etoposide or paclitaxel were synergistic, altering cell cycle distribution and increasing cell death, this provides rationale for testing combinatorial chemotherapy with fulvestrant as a novel therapeutic strategy for patients with advanced breast cancer.
Fil: Dolfi, Sonia C.. Rutgers Cancer Institute of New Jersey; Estados Unidos
Fil: Jager, Adriana Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Medina, Daniel J.. Rutgers Cancer Institute of New Jersey; Estados Unidos
Fil: Haffty, Bruce G.. Rutgers Cancer Institute of New Jersey; Estados Unidos
Fil: Yang, Jin Ming. State University of Pennsylvania; Estados Unidos
Fil: Hirshfield, Kim M.. Rutgers Cancer Institute of New Jersey; Estados Unidos
Materia
Fulvestrant
Mdm2
Chemotherapy
Estrogen Receptor
Breast Cancer
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:11336/33148
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/33148
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Fulvestrant treatment alters MDM2 protein turnover and sensitivity of human breast carcinoma cells to chemotherapeutic drugsDolfi, Sonia C.Jager, Adriana ValeriaMedina, Daniel J.Haffty, Bruce G.Yang, Jin MingHirshfield, Kim M.FulvestrantMdm2ChemotherapyEstrogen ReceptorBreast Cancerhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3The human homologue of mouse double minute 2 (MDM2) is overexpressed in tumors and contributes to tumorigenesis through inhibition of p53 activity. We investigated the effect of the anti-estrogen fulvestrant on MDM2 expression and sensitivity of estrogen receptor positive human breast cancer cell lines to chemotherapeutics. Fulvestrant down-regulated MDM2 through increased protein turnover. Fulvestrant blocked estrogen-dependent up-regulation of MDM2 and decreased basal expression of MDM2 in the absence of estradiol. As combinations of fulvestrant with doxorubicin, etoposide or paclitaxel were synergistic, altering cell cycle distribution and increasing cell death, this provides rationale for testing combinatorial chemotherapy with fulvestrant as a novel therapeutic strategy for patients with advanced breast cancer.Fil: Dolfi, Sonia C.. Rutgers Cancer Institute of New Jersey; Estados UnidosFil: Jager, Adriana Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Medina, Daniel J.. Rutgers Cancer Institute of New Jersey; Estados UnidosFil: Haffty, Bruce G.. Rutgers Cancer Institute of New Jersey; Estados UnidosFil: Yang, Jin Ming. State University of Pennsylvania; Estados UnidosFil: Hirshfield, Kim M.. Rutgers Cancer Institute of New Jersey; Estados UnidosElsevier Ireland2014-08info: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/11336/33148Dolfi, Sonia C.; Jager, Adriana Valeria; Medina, Daniel J.; Haffty, Bruce G.; Yang, Jin Ming; et al.; Fulvestrant treatment alters MDM2 protein turnover and sensitivity of human breast carcinoma cells to chemotherapeutic drugs; Elsevier Ireland; Cancer Letters; 350; 8-2014; 52-600304-3835CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0304383514002158info:eu-repo/semantics/altIdentifier/doi/10.1016/j.canlet.2014.04.009info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:07:51Zoai:ri.conicet.gov.ar:11336/33148instacron: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:34982025-10-15 15:07:51.416CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Fulvestrant treatment alters MDM2 protein turnover and sensitivity of human breast carcinoma cells to chemotherapeutic drugs
title Fulvestrant treatment alters MDM2 protein turnover and sensitivity of human breast carcinoma cells to chemotherapeutic drugs
spellingShingle Fulvestrant treatment alters MDM2 protein turnover and sensitivity of human breast carcinoma cells to chemotherapeutic drugs
Dolfi, Sonia C.
Fulvestrant
Mdm2
Chemotherapy
Estrogen Receptor
Breast Cancer
title_short Fulvestrant treatment alters MDM2 protein turnover and sensitivity of human breast carcinoma cells to chemotherapeutic drugs
title_full Fulvestrant treatment alters MDM2 protein turnover and sensitivity of human breast carcinoma cells to chemotherapeutic drugs
title_fullStr Fulvestrant treatment alters MDM2 protein turnover and sensitivity of human breast carcinoma cells to chemotherapeutic drugs
title_full_unstemmed Fulvestrant treatment alters MDM2 protein turnover and sensitivity of human breast carcinoma cells to chemotherapeutic drugs
title_sort Fulvestrant treatment alters MDM2 protein turnover and sensitivity of human breast carcinoma cells to chemotherapeutic drugs
dc.creator.none.fl_str_mv Dolfi, Sonia C.
Jager, Adriana Valeria
Medina, Daniel J.
Haffty, Bruce G.
Yang, Jin Ming
Hirshfield, Kim M.
author Dolfi, Sonia C.
author_facet Dolfi, Sonia C.
Jager, Adriana Valeria
Medina, Daniel J.
Haffty, Bruce G.
Yang, Jin Ming
Hirshfield, Kim M.
author_role author
author2 Jager, Adriana Valeria
Medina, Daniel J.
Haffty, Bruce G.
Yang, Jin Ming
Hirshfield, Kim M.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Fulvestrant
Mdm2
Chemotherapy
Estrogen Receptor
Breast Cancer
topic Fulvestrant
Mdm2
Chemotherapy
Estrogen Receptor
Breast Cancer
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The human homologue of mouse double minute 2 (MDM2) is overexpressed in tumors and contributes to tumorigenesis through inhibition of p53 activity. We investigated the effect of the anti-estrogen fulvestrant on MDM2 expression and sensitivity of estrogen receptor positive human breast cancer cell lines to chemotherapeutics. Fulvestrant down-regulated MDM2 through increased protein turnover. Fulvestrant blocked estrogen-dependent up-regulation of MDM2 and decreased basal expression of MDM2 in the absence of estradiol. As combinations of fulvestrant with doxorubicin, etoposide or paclitaxel were synergistic, altering cell cycle distribution and increasing cell death, this provides rationale for testing combinatorial chemotherapy with fulvestrant as a novel therapeutic strategy for patients with advanced breast cancer.
Fil: Dolfi, Sonia C.. Rutgers Cancer Institute of New Jersey; Estados Unidos
Fil: Jager, Adriana Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Medina, Daniel J.. Rutgers Cancer Institute of New Jersey; Estados Unidos
Fil: Haffty, Bruce G.. Rutgers Cancer Institute of New Jersey; Estados Unidos
Fil: Yang, Jin Ming. State University of Pennsylvania; Estados Unidos
Fil: Hirshfield, Kim M.. Rutgers Cancer Institute of New Jersey; Estados Unidos
description The human homologue of mouse double minute 2 (MDM2) is overexpressed in tumors and contributes to tumorigenesis through inhibition of p53 activity. We investigated the effect of the anti-estrogen fulvestrant on MDM2 expression and sensitivity of estrogen receptor positive human breast cancer cell lines to chemotherapeutics. Fulvestrant down-regulated MDM2 through increased protein turnover. Fulvestrant blocked estrogen-dependent up-regulation of MDM2 and decreased basal expression of MDM2 in the absence of estradiol. As combinations of fulvestrant with doxorubicin, etoposide or paclitaxel were synergistic, altering cell cycle distribution and increasing cell death, this provides rationale for testing combinatorial chemotherapy with fulvestrant as a novel therapeutic strategy for patients with advanced breast cancer.
publishDate 2014
dc.date.none.fl_str_mv 2014-08
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/11336/33148
Dolfi, Sonia C.; Jager, Adriana Valeria; Medina, Daniel J.; Haffty, Bruce G.; Yang, Jin Ming; et al.; Fulvestrant treatment alters MDM2 protein turnover and sensitivity of human breast carcinoma cells to chemotherapeutic drugs; Elsevier Ireland; Cancer Letters; 350; 8-2014; 52-60
0304-3835
CONICET Digital
CONICET
url http://hdl.handle.net/11336/33148
identifier_str_mv Dolfi, Sonia C.; Jager, Adriana Valeria; Medina, Daniel J.; Haffty, Bruce G.; Yang, Jin Ming; et al.; Fulvestrant treatment alters MDM2 protein turnover and sensitivity of human breast carcinoma cells to chemotherapeutic drugs; Elsevier Ireland; Cancer Letters; 350; 8-2014; 52-60
0304-3835
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.sciencedirect.com/science/article/pii/S0304383514002158
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.canlet.2014.04.009
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.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
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
_version_ 1846083223731306496
score 13.22299

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