Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage

Autores
Reeder, A.; Attar, M.; Nazario, L.; Bathula, C.; Zhang, A.; Hochbaum, Daniel; Roy, E.; Cooper, K. L.; Oesterreich, S.; Davidson, N. E.; Neumann, C. A.; Flint, M. S.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: The mechanisms by which stress hormones impact triple-negative breast cancer (TNBC) etiology and treatment are unclear. We have previously shown that stress hormones, cortisol, and catecholamines induce rapid DNA damage and impact DNA repair in NIH 3T3 fibroblasts. This study investigates whether stress hormones increase DNA damage in breast cancer cells and if this impacts drug efficacy. Methods: We first screened a panel of 39 breast cancer cell lines for expression of adrenergic and glucocorticoid receptors and examined if stress hormones induce DNA damage and alter cell cycle regulation in vitro. A TNBC xenograft model was used to assess the impact of restraint stress on tumour growth and chemosensitivity to paclitaxel. Results: We found that stress hormones induced DNA damage, phosphorylation of ATR, which was accompanied by an up-regulation of the G1 cell kinase inhibitor p21 and a cell cycle halt of TNBCs in the G1 phase. p21 knockdown abrogated G1 arrest by stress hormones. We also demonstrated that stress significantly decreased efficacy of paclitaxel. Conclusion: We describe a novel mechanism through which stress hormones can induce drug resistance to paclitaxel, which may have profound implications for treating drug resistance in patients with TNBC.
Fil: Reeder, A.. University of Pittsburgh; Estados Unidos
Fil: Attar, M.. University of Pittsburgh; Estados Unidos
Fil: Nazario, L.. University of Pittsburgh; Estados Unidos
Fil: Bathula, C.. University of Pittsburgh; Estados Unidos
Fil: Zhang, A.. University of Pittsburgh; Estados Unidos
Fil: Hochbaum, Daniel. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Roy, E.. University of Pittsburgh; Estados Unidos
Fil: Cooper, K. L.. University of Pittsburgh; Estados Unidos
Fil: Oesterreich, S.. University of Pittsburgh; Estados Unidos
Fil: Davidson, N. E.. University of Pittsburgh; Estados Unidos
Fil: Neumann, C. A.. University of Pittsburgh; Estados Unidos
Fil: Flint, M. S.. University of Pittsburgh; Estados Unidos. University of Brighton; Reino Unido
Materia
BREAST CANCER
CORTISOL
EPINEPHRINE
PACLITAXEL
STRESS
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:11336/84951
Acceder
id CONICETDig_957e28ce55c3c29031c620ce87234a88
oai_identifier_str oai:ri.conicet.gov.ar:11336/84951
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damageReeder, A.Attar, M.Nazario, L.Bathula, C.Zhang, A.Hochbaum, DanielRoy, E.Cooper, K. L.Oesterreich, S.Davidson, N. E.Neumann, C. A.Flint, M. S.BREAST CANCERCORTISOLEPINEPHRINEPACLITAXELSTRESShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: The mechanisms by which stress hormones impact triple-negative breast cancer (TNBC) etiology and treatment are unclear. We have previously shown that stress hormones, cortisol, and catecholamines induce rapid DNA damage and impact DNA repair in NIH 3T3 fibroblasts. This study investigates whether stress hormones increase DNA damage in breast cancer cells and if this impacts drug efficacy. Methods: We first screened a panel of 39 breast cancer cell lines for expression of adrenergic and glucocorticoid receptors and examined if stress hormones induce DNA damage and alter cell cycle regulation in vitro. A TNBC xenograft model was used to assess the impact of restraint stress on tumour growth and chemosensitivity to paclitaxel. Results: We found that stress hormones induced DNA damage, phosphorylation of ATR, which was accompanied by an up-regulation of the G1 cell kinase inhibitor p21 and a cell cycle halt of TNBCs in the G1 phase. p21 knockdown abrogated G1 arrest by stress hormones. We also demonstrated that stress significantly decreased efficacy of paclitaxel. Conclusion: We describe a novel mechanism through which stress hormones can induce drug resistance to paclitaxel, which may have profound implications for treating drug resistance in patients with TNBC.Fil: Reeder, A.. University of Pittsburgh; Estados UnidosFil: Attar, M.. University of Pittsburgh; Estados UnidosFil: Nazario, L.. University of Pittsburgh; Estados UnidosFil: Bathula, C.. University of Pittsburgh; Estados UnidosFil: Zhang, A.. University of Pittsburgh; Estados UnidosFil: Hochbaum, Daniel. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roy, E.. University of Pittsburgh; Estados UnidosFil: Cooper, K. L.. University of Pittsburgh; Estados UnidosFil: Oesterreich, S.. University of Pittsburgh; Estados UnidosFil: Davidson, N. E.. University of Pittsburgh; Estados UnidosFil: Neumann, C. A.. University of Pittsburgh; Estados UnidosFil: Flint, M. S.. University of Pittsburgh; Estados Unidos. University of Brighton; Reino UnidoNature Publishing Group2015-04info: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/11336/84951Reeder, A.; Attar, M.; Nazario, L.; Bathula, C.; Zhang, A.; et al.; Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage; Nature Publishing Group; British Journal Of Cancer; 112; 9; 4-2015; 1461-14700007-0920CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/bjc.2015.133info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/bjc2015133info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453678/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T11:25:43Zoai:ri.conicet.gov.ar:11336/84951instacron: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:34982025-09-17 11:25:43.546CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage
title Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage
spellingShingle Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage
Reeder, A.
BREAST CANCER
CORTISOL
EPINEPHRINE
PACLITAXEL
STRESS
title_short Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage
title_full Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage
title_fullStr Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage
title_full_unstemmed Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage
title_sort Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage
dc.creator.none.fl_str_mv Reeder, A.
Attar, M.
Nazario, L.
Bathula, C.
Zhang, A.
Hochbaum, Daniel
Roy, E.
Cooper, K. L.
Oesterreich, S.
Davidson, N. E.
Neumann, C. A.
Flint, M. S.
author Reeder, A.
author_facet Reeder, A.
Attar, M.
Nazario, L.
Bathula, C.
Zhang, A.
Hochbaum, Daniel
Roy, E.
Cooper, K. L.
Oesterreich, S.
Davidson, N. E.
Neumann, C. A.
Flint, M. S.
author_role author
author2 Attar, M.
Nazario, L.
Bathula, C.
Zhang, A.
Hochbaum, Daniel
Roy, E.
Cooper, K. L.
Oesterreich, S.
Davidson, N. E.
Neumann, C. A.
Flint, M. S.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BREAST CANCER
CORTISOL
EPINEPHRINE
PACLITAXEL
STRESS
topic BREAST CANCER
CORTISOL
EPINEPHRINE
PACLITAXEL
STRESS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background: The mechanisms by which stress hormones impact triple-negative breast cancer (TNBC) etiology and treatment are unclear. We have previously shown that stress hormones, cortisol, and catecholamines induce rapid DNA damage and impact DNA repair in NIH 3T3 fibroblasts. This study investigates whether stress hormones increase DNA damage in breast cancer cells and if this impacts drug efficacy. Methods: We first screened a panel of 39 breast cancer cell lines for expression of adrenergic and glucocorticoid receptors and examined if stress hormones induce DNA damage and alter cell cycle regulation in vitro. A TNBC xenograft model was used to assess the impact of restraint stress on tumour growth and chemosensitivity to paclitaxel. Results: We found that stress hormones induced DNA damage, phosphorylation of ATR, which was accompanied by an up-regulation of the G1 cell kinase inhibitor p21 and a cell cycle halt of TNBCs in the G1 phase. p21 knockdown abrogated G1 arrest by stress hormones. We also demonstrated that stress significantly decreased efficacy of paclitaxel. Conclusion: We describe a novel mechanism through which stress hormones can induce drug resistance to paclitaxel, which may have profound implications for treating drug resistance in patients with TNBC.
Fil: Reeder, A.. University of Pittsburgh; Estados Unidos
Fil: Attar, M.. University of Pittsburgh; Estados Unidos
Fil: Nazario, L.. University of Pittsburgh; Estados Unidos
Fil: Bathula, C.. University of Pittsburgh; Estados Unidos
Fil: Zhang, A.. University of Pittsburgh; Estados Unidos
Fil: Hochbaum, Daniel. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Roy, E.. University of Pittsburgh; Estados Unidos
Fil: Cooper, K. L.. University of Pittsburgh; Estados Unidos
Fil: Oesterreich, S.. University of Pittsburgh; Estados Unidos
Fil: Davidson, N. E.. University of Pittsburgh; Estados Unidos
Fil: Neumann, C. A.. University of Pittsburgh; Estados Unidos
Fil: Flint, M. S.. University of Pittsburgh; Estados Unidos. University of Brighton; Reino Unido
description Background: The mechanisms by which stress hormones impact triple-negative breast cancer (TNBC) etiology and treatment are unclear. We have previously shown that stress hormones, cortisol, and catecholamines induce rapid DNA damage and impact DNA repair in NIH 3T3 fibroblasts. This study investigates whether stress hormones increase DNA damage in breast cancer cells and if this impacts drug efficacy. Methods: We first screened a panel of 39 breast cancer cell lines for expression of adrenergic and glucocorticoid receptors and examined if stress hormones induce DNA damage and alter cell cycle regulation in vitro. A TNBC xenograft model was used to assess the impact of restraint stress on tumour growth and chemosensitivity to paclitaxel. Results: We found that stress hormones induced DNA damage, phosphorylation of ATR, which was accompanied by an up-regulation of the G1 cell kinase inhibitor p21 and a cell cycle halt of TNBCs in the G1 phase. p21 knockdown abrogated G1 arrest by stress hormones. We also demonstrated that stress significantly decreased efficacy of paclitaxel. Conclusion: We describe a novel mechanism through which stress hormones can induce drug resistance to paclitaxel, which may have profound implications for treating drug resistance in patients with TNBC.
publishDate 2015
dc.date.none.fl_str_mv 2015-04
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/11336/84951
Reeder, A.; Attar, M.; Nazario, L.; Bathula, C.; Zhang, A.; et al.; Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage; Nature Publishing Group; British Journal Of Cancer; 112; 9; 4-2015; 1461-1470
0007-0920
CONICET Digital
CONICET
url http://hdl.handle.net/11336/84951
identifier_str_mv Reeder, A.; Attar, M.; Nazario, L.; Bathula, C.; Zhang, A.; et al.; Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage; Nature Publishing Group; British Journal Of Cancer; 112; 9; 4-2015; 1461-1470
0007-0920
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/bjc.2015.133
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/bjc2015133
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453678/
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 Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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 13.001348

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