The proapoptotic gene interferon regulatory factor-1 mediates the antiproliferative outcome of paired box 2 gene and tamoxifen

Càncer de mama; Marcadors pronòstics

Detalles Bibliográficos
Autores: Wang, Shixiong, Somisetty, Venkata S., Bai, Baoyan, Chernukhin, Igor, Niskanen, Henri, Kaikkonen, Minna U., Bellet Ezquerra, Meritxell
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:11351/6516
Acceso en línea:https://hdl.handle.net/11351/6516
http://hdl.handle.net/11351/6516
Access Level:acceso abierto
Palabra clave:Mama - Càncer - Tractament
Regulació genètica
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Gene Expression Regulation, Neoplastic
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::regulación de la expresión génica neoplásica
id ES_29dc48846fc76493fb8ecb4f4a9cf29f
oai_identifier_str oai:recercat.cat:11351/6516
network_acronym_str ES
network_name_str España
repository_id_str
spelling The proapoptotic gene interferon regulatory factor-1 mediates the antiproliferative outcome of paired box 2 gene and tamoxifenWang, ShixiongSomisetty, Venkata S.Bai, BaoyanChernukhin, IgorNiskanen, HenriKaikkonen, Minna U.Bellet Ezquerra, MeritxellMama - Càncer - TractamentRegulació genèticaDISEASES::Neoplasms::Neoplasms by Site::Breast NeoplasmsOther subheadings::Other subheadings::Other subheadings::/drug therapyPHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Gene Expression Regulation, NeoplasticENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mamaOtros calificadores::Otros calificadores::Otros calificadores::/farmacoterapiaFENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::regulación de la expresión génica neoplásicaCàncer de mama; Marcadors pronòsticsCáncer de mama; Marcadores de pronósticoBreast cancer; Prognostic markersTamoxifen is the most prescribed selective estrogen receptor (ER) modulator in patients with ER-positive breast cancers. Tamoxifen requires the transcription factor paired box 2 protein (PAX2) to repress the transcription of ERBB2/HER2. Now, we identified that PAX2 inhibits cell growth of ER+/HER2− tumor cells in a dose-dependent manner. Moreover, we have identified that cell growth inhibition can be achieved by expressing moderate levels of PAX2 in combination with tamoxifen treatment. Global run-on sequencing of cells overexpressing PAX2, when coupled with PAX2 ChIP-seq, identified common targets regulated by both PAX2 and tamoxifen. The data revealed that PAX2 can inhibit estrogen-induced gene transcription and this effect is enhanced by tamoxifen, suggesting that they converge on repression of the same targets. Moreover, PAX2 and tamoxifen have an additive effect and both induce coding genes and enhancer RNAs (eRNAs). PAX2–tamoxifen upregulated genes are also enriched with PAX2 eRNAs. The enrichment of eRNAs is associated with the highest expression of genes that positivity regulate apoptotic processes. In luminal tumors, the expression of a subset of these proapoptotic genes predicts good outcome and their expression are significantly reduced in tumors of patients with relapse to tamoxifen treatment. Mechanistically, PAX2 and tamoxifen coexert an antitumoral effect by maintaining high levels of transcription of tumor suppressors that promote cell death. The apoptotic effect is mediated in large part by the gene interferon regulatory factor 1. Altogether, we conclude that PAX2 contributes to better clinical outcome in tamoxifen treated ER-positive breast cancer patients by repressing estrogen signaling and inducing cell death related pathways.Springer NatureInstitut Català de la Salut[Wang S, Somisetty VS, Bai B] Cell Cycle Regulations Group, Nordic EMBL Partnership, Centre for Molecular Medicine Norway (NCMM), University of Oslo, Blindern, P.O. 1137, 0318 Oslo, Norway. [Chernukhin I] Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK. [Niskanen H, Kaikkonen MU] A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, 70211 Kuopio, Finland. [Bellet M] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202120212020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttps://hdl.handle.net/11351/6516http://hdl.handle.net/11351/6516Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésOncogene;39(40)https://doi.org/10.1038/s41388-020-01435-4Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/65162026-05-29T05:05:01Z
dc.title.none.fl_str_mv The proapoptotic gene interferon regulatory factor-1 mediates the antiproliferative outcome of paired box 2 gene and tamoxifen
title The proapoptotic gene interferon regulatory factor-1 mediates the antiproliferative outcome of paired box 2 gene and tamoxifen
spellingShingle The proapoptotic gene interferon regulatory factor-1 mediates the antiproliferative outcome of paired box 2 gene and tamoxifen
Wang, Shixiong
Mama - Càncer - Tractament
Regulació genètica
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Gene Expression Regulation, Neoplastic
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::regulación de la expresión génica neoplásica
title_short The proapoptotic gene interferon regulatory factor-1 mediates the antiproliferative outcome of paired box 2 gene and tamoxifen
title_full The proapoptotic gene interferon regulatory factor-1 mediates the antiproliferative outcome of paired box 2 gene and tamoxifen
title_fullStr The proapoptotic gene interferon regulatory factor-1 mediates the antiproliferative outcome of paired box 2 gene and tamoxifen
title_full_unstemmed The proapoptotic gene interferon regulatory factor-1 mediates the antiproliferative outcome of paired box 2 gene and tamoxifen
title_sort The proapoptotic gene interferon regulatory factor-1 mediates the antiproliferative outcome of paired box 2 gene and tamoxifen
dc.creator.none.fl_str_mv Wang, Shixiong
Somisetty, Venkata S.
Bai, Baoyan
Chernukhin, Igor
Niskanen, Henri
Kaikkonen, Minna U.
Bellet Ezquerra, Meritxell
author Wang, Shixiong
author_facet Wang, Shixiong
Somisetty, Venkata S.
Bai, Baoyan
Chernukhin, Igor
Niskanen, Henri
Kaikkonen, Minna U.
Bellet Ezquerra, Meritxell
author_role author
author2 Somisetty, Venkata S.
Bai, Baoyan
Chernukhin, Igor
Niskanen, Henri
Kaikkonen, Minna U.
Bellet Ezquerra, Meritxell
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Wang S, Somisetty VS, Bai B] Cell Cycle Regulations Group, Nordic EMBL Partnership, Centre for Molecular Medicine Norway (NCMM), University of Oslo, Blindern, P.O. 1137, 0318 Oslo, Norway. [Chernukhin I] Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK. [Niskanen H, Kaikkonen MU] A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, 70211 Kuopio, Finland. [Bellet M] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Mama - Càncer - Tractament
Regulació genètica
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Gene Expression Regulation, Neoplastic
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::regulación de la expresión génica neoplásica
topic Mama - Càncer - Tractament
Regulació genètica
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Gene Expression Regulation, Neoplastic
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::regulación de la expresión génica neoplásica
description Càncer de mama; Marcadors pronòstics
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/6516
http://hdl.handle.net/11351/6516
url https://hdl.handle.net/11351/6516
http://hdl.handle.net/11351/6516
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Oncogene;39(40)
https://doi.org/10.1038/s41388-020-01435-4
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv Scientia
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869405034368729088
score 15,811543

Similares en LA Referencia