Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells

Autores
Goard, Carolyn A.; Chan Seng Yue, Michelle; Mullen, Peter J.; Quiroga, Ariel Dario; Wasylishen, Amanda R.; Clendening, James W.; Sendorek, Dorota H. S.; Haider, Syed; Lehner, Richard; Boutros, Paul C.; Penn, Linda Z.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Statins, routinely used to treat hypercholesterolemia, selectively induce apoptosis in some tumor cells by inhibiting the mevalonate pathway. Recent clinical studies suggest that a subset of breast tumors is particularly susceptible to lipophilic statins, such as fluvastatin. To quickly advance statins as effective anticancer agents for breast cancer treatment, it is critical to identify the molecular features defining this sensitive subset. We have therefore characterized fluvastatin sensitivity by MTT assay in a panel of 19 breast cell lines that reflect the molecular diversity of breast cancer, and have evaluated the association of sensitivity with several clinicopathological and molecular features. A wide range of fluvastatin sensitivity was observed across breast tumor cell lines, with fluvastatin triggering cell death in a subset of sensitive cell lines. Fluvastatin sensitivity was associated with an estrogen receptor alpha (ERa)-negative, basal-like tumor subtype, features that can be scored with routine and/or strong preclinical diagnostics. To ascertain additional candidate sensitivity-associated molecular features, we mined publicly available gene expression datasets, identifying genes encoding regulators of mevalonate production, nonsterol lipid homeostasis, and global cellular metabolism, including the oncogene MYC. Further exploration of this data allowed us to generate a 10-gene mRNA abundance signature predictive of fluvastatin sensitivity, which showed preliminary validation in an independent set of breast tumor cell lines. Here, we have therefore identified several candidate predictors of sensitivity to fluvastatin treatment in breast cancer, which warrant further preclinical and clinical evaluation.
Fil: Goard, Carolyn A.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; Canadá
Fil: Chan Seng Yue, Michelle . University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; Canadá
Fil: Mullen, Peter J.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá
Fil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina. University of Alberta; Canadá
Fil: Wasylishen, Amanda R.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; Canadá
Fil: Clendening, James W.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; Canadá
Fil: Sendorek, Dorota H. S.. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; Canadá
Fil: Haider, Syed. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; Canadá
Fil: Lehner, Richard. University of Alberta; Canadá
Fil: Boutros, Paul C.. University Of Toronto; Canadá. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; Canadá
Fil: Penn, Linda Z.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; Canadá
Materia
Statin
Fluvastatin
Breast Cancer
Estrogen Receptor
Gene Expression
Drug Sensitivity
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:11336/6118
Acceder
id CONICETDig_4a3ed93ab0493672e363cd6087b6e2ce
oai_identifier_str oai:ri.conicet.gov.ar:11336/6118
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cellsGoard, Carolyn A.Chan Seng Yue, Michelle Mullen, Peter J.Quiroga, Ariel DarioWasylishen, Amanda R.Clendening, James W.Sendorek, Dorota H. S.Haider, SyedLehner, RichardBoutros, Paul C.Penn, Linda Z.StatinFluvastatinBreast CancerEstrogen ReceptorGene ExpressionDrug Sensitivityhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Statins, routinely used to treat hypercholesterolemia, selectively induce apoptosis in some tumor cells by inhibiting the mevalonate pathway. Recent clinical studies suggest that a subset of breast tumors is particularly susceptible to lipophilic statins, such as fluvastatin. To quickly advance statins as effective anticancer agents for breast cancer treatment, it is critical to identify the molecular features defining this sensitive subset. We have therefore characterized fluvastatin sensitivity by MTT assay in a panel of 19 breast cell lines that reflect the molecular diversity of breast cancer, and have evaluated the association of sensitivity with several clinicopathological and molecular features. A wide range of fluvastatin sensitivity was observed across breast tumor cell lines, with fluvastatin triggering cell death in a subset of sensitive cell lines. Fluvastatin sensitivity was associated with an estrogen receptor alpha (ERa)-negative, basal-like tumor subtype, features that can be scored with routine and/or strong preclinical diagnostics. To ascertain additional candidate sensitivity-associated molecular features, we mined publicly available gene expression datasets, identifying genes encoding regulators of mevalonate production, nonsterol lipid homeostasis, and global cellular metabolism, including the oncogene MYC. Further exploration of this data allowed us to generate a 10-gene mRNA abundance signature predictive of fluvastatin sensitivity, which showed preliminary validation in an independent set of breast tumor cell lines. Here, we have therefore identified several candidate predictors of sensitivity to fluvastatin treatment in breast cancer, which warrant further preclinical and clinical evaluation.Fil: Goard, Carolyn A.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; CanadáFil: Chan Seng Yue, Michelle . University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; CanadáFil: Mullen, Peter J.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; CanadáFil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina. University of Alberta; CanadáFil: Wasylishen, Amanda R.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; CanadáFil: Clendening, James W.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; CanadáFil: Sendorek, Dorota H. S.. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; CanadáFil: Haider, Syed. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; CanadáFil: Lehner, Richard. University of Alberta; CanadáFil: Boutros, Paul C.. University Of Toronto; Canadá. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; CanadáFil: Penn, Linda Z.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; CanadáSpringer2014-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/6118Goard, Carolyn A.; Chan Seng Yue, Michelle ; Mullen, Peter J.; Quiroga, Ariel Dario; Wasylishen, Amanda R.; et al.; Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells; Springer; Breast Cancer Research And Treatment; 143; 2; 1-2014; 301-3120167-6806enginfo:eu-repo/semantics/altIdentifier/url/http://link.springer.com/article/10.1007%2Fs10549-013-2800-yinfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/doi/10.1007/s10549-013-2800-yinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:49:29Zoai:ri.conicet.gov.ar:11336/6118instacron: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:34982025-09-29 09:49:29.625CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells
title Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells
spellingShingle Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells
Goard, Carolyn A.
Statin
Fluvastatin
Breast Cancer
Estrogen Receptor
Gene Expression
Drug Sensitivity
title_short Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells
title_full Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells
title_fullStr Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells
title_full_unstemmed Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells
title_sort Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells
dc.creator.none.fl_str_mv Goard, Carolyn A.
Chan Seng Yue, Michelle
Mullen, Peter J.
Quiroga, Ariel Dario
Wasylishen, Amanda R.
Clendening, James W.
Sendorek, Dorota H. S.
Haider, Syed
Lehner, Richard
Boutros, Paul C.
Penn, Linda Z.
author Goard, Carolyn A.
author_facet Goard, Carolyn A.
Chan Seng Yue, Michelle
Mullen, Peter J.
Quiroga, Ariel Dario
Wasylishen, Amanda R.
Clendening, James W.
Sendorek, Dorota H. S.
Haider, Syed
Lehner, Richard
Boutros, Paul C.
Penn, Linda Z.
author_role author
author2 Chan Seng Yue, Michelle
Mullen, Peter J.
Quiroga, Ariel Dario
Wasylishen, Amanda R.
Clendening, James W.
Sendorek, Dorota H. S.
Haider, Syed
Lehner, Richard
Boutros, Paul C.
Penn, Linda Z.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Statin
Fluvastatin
Breast Cancer
Estrogen Receptor
Gene Expression
Drug Sensitivity
topic Statin
Fluvastatin
Breast Cancer
Estrogen Receptor
Gene Expression
Drug Sensitivity
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Statins, routinely used to treat hypercholesterolemia, selectively induce apoptosis in some tumor cells by inhibiting the mevalonate pathway. Recent clinical studies suggest that a subset of breast tumors is particularly susceptible to lipophilic statins, such as fluvastatin. To quickly advance statins as effective anticancer agents for breast cancer treatment, it is critical to identify the molecular features defining this sensitive subset. We have therefore characterized fluvastatin sensitivity by MTT assay in a panel of 19 breast cell lines that reflect the molecular diversity of breast cancer, and have evaluated the association of sensitivity with several clinicopathological and molecular features. A wide range of fluvastatin sensitivity was observed across breast tumor cell lines, with fluvastatin triggering cell death in a subset of sensitive cell lines. Fluvastatin sensitivity was associated with an estrogen receptor alpha (ERa)-negative, basal-like tumor subtype, features that can be scored with routine and/or strong preclinical diagnostics. To ascertain additional candidate sensitivity-associated molecular features, we mined publicly available gene expression datasets, identifying genes encoding regulators of mevalonate production, nonsterol lipid homeostasis, and global cellular metabolism, including the oncogene MYC. Further exploration of this data allowed us to generate a 10-gene mRNA abundance signature predictive of fluvastatin sensitivity, which showed preliminary validation in an independent set of breast tumor cell lines. Here, we have therefore identified several candidate predictors of sensitivity to fluvastatin treatment in breast cancer, which warrant further preclinical and clinical evaluation.
Fil: Goard, Carolyn A.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; Canadá
Fil: Chan Seng Yue, Michelle . University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; Canadá
Fil: Mullen, Peter J.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá
Fil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina. University of Alberta; Canadá
Fil: Wasylishen, Amanda R.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; Canadá
Fil: Clendening, James W.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; Canadá
Fil: Sendorek, Dorota H. S.. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; Canadá
Fil: Haider, Syed. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; Canadá
Fil: Lehner, Richard. University of Alberta; Canadá
Fil: Boutros, Paul C.. University Of Toronto; Canadá. Ontario Institute of Cancer Research. Informatics and Biocomputing Platform; Canadá
Fil: Penn, Linda Z.. University Health Network. Princess Margaret Cancer Centre. Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research; Canadá. University Of Toronto; Canadá
description Statins, routinely used to treat hypercholesterolemia, selectively induce apoptosis in some tumor cells by inhibiting the mevalonate pathway. Recent clinical studies suggest that a subset of breast tumors is particularly susceptible to lipophilic statins, such as fluvastatin. To quickly advance statins as effective anticancer agents for breast cancer treatment, it is critical to identify the molecular features defining this sensitive subset. We have therefore characterized fluvastatin sensitivity by MTT assay in a panel of 19 breast cell lines that reflect the molecular diversity of breast cancer, and have evaluated the association of sensitivity with several clinicopathological and molecular features. A wide range of fluvastatin sensitivity was observed across breast tumor cell lines, with fluvastatin triggering cell death in a subset of sensitive cell lines. Fluvastatin sensitivity was associated with an estrogen receptor alpha (ERa)-negative, basal-like tumor subtype, features that can be scored with routine and/or strong preclinical diagnostics. To ascertain additional candidate sensitivity-associated molecular features, we mined publicly available gene expression datasets, identifying genes encoding regulators of mevalonate production, nonsterol lipid homeostasis, and global cellular metabolism, including the oncogene MYC. Further exploration of this data allowed us to generate a 10-gene mRNA abundance signature predictive of fluvastatin sensitivity, which showed preliminary validation in an independent set of breast tumor cell lines. Here, we have therefore identified several candidate predictors of sensitivity to fluvastatin treatment in breast cancer, which warrant further preclinical and clinical evaluation.
publishDate 2014
dc.date.none.fl_str_mv 2014-01
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/11336/6118
Goard, Carolyn A.; Chan Seng Yue, Michelle ; Mullen, Peter J.; Quiroga, Ariel Dario; Wasylishen, Amanda R.; et al.; Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells; Springer; Breast Cancer Research And Treatment; 143; 2; 1-2014; 301-312
0167-6806
url http://hdl.handle.net/11336/6118
identifier_str_mv Goard, Carolyn A.; Chan Seng Yue, Michelle ; Mullen, Peter J.; Quiroga, Ariel Dario; Wasylishen, Amanda R.; et al.; Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells; Springer; Breast Cancer Research And Treatment; 143; 2; 1-2014; 301-312
0167-6806
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://link.springer.com/article/10.1007%2Fs10549-013-2800-y
info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/doi/10.1007/s10549-013-2800-y
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
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
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 13.070432

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