Multimodal assessment of estrogen receptor mRNA profiles to quantify estrogen pathway activity in breast tumors

Show simple item record Muthukaruppan, Anitadevi en Lasham, Annette en Woad, KJ en Black, MA en Blenkiron, Cherie en Miller, LD en Harris, G en McCarthy, N en Findlay, Michael en Shelling, Andrew en Print, Cristin en 2017-10-08T23:23:35Z en 2017-04 en
dc.identifier.citation Clinical Breast Cancer 17(2):139-153 Apr 2017 en
dc.identifier.issn 1526-8209 en
dc.identifier.uri en
dc.description.abstract Molecular markers have transformed our understanding of the heterogeneity of breast cancer and have allowed the identification of genomic profiles of estrogen receptor (ER)-α signaling. However, our understanding of the transcriptional profiles of ER signaling remains inadequate. Therefore, we sought to identify the genomic indicators of ER pathway activity that could supplement traditional immunohistochemical (IHC) assessments of ER status to better understand ER signaling in the breast tumors of individual patients.We reduced ESR1 (gene encoding the ER-α protein) mRNA levels using small interfering RNA in ER+ MCF7 breast cancer cells and assayed for transcriptional changes using Affymetrix HG U133 Plus 2.0 arrays. We also compared 1034 ER+ and ER- breast tumors from publicly available microarray data. The principal components of ER activity generated from these analyses and from other published estrogen signatures were compared with ESR1 expression, ER-α IHC, and patient survival.Genes differentially expressed in both analyses were associated with ER-α IHC and ESR1 mRNA expression. They were also significantly enriched for estrogen-driven molecular pathways associated with ESR1, cyclin D1 (CCND1), MYC (v-myc avian myelocytomatosis viral oncogene homolog), and NFKB (nuclear factor kappa B). Despite their differing constituent genes, the principal components generated from these new analyses and from previously published ER-associated gene lists were all associated with each other and with the survival of patients with breast cancer treated with endocrine therapies.A biomarker of ER-α pathway activity, generated using ESR1-responsive mRNAs in MCF7 cells, when used alongside ER-α IHC and ESR1 mRNA expression, could provide a method for further stratification of patients and add insight into ER pathway activity in these patients. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.publisher Elsevier en
dc.relation.ispartofseries Clinical Breast Cancer en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
dc.rights.uri en
dc.rights.uri en
dc.subject Humans en
dc.subject Breast Neoplasms en
dc.subject Carrier Proteins en
dc.subject Receptors, Estrogen en
dc.subject Estrogen Receptor alpha en
dc.subject RNA, Small Interfering en
dc.subject RNA, Messenger en
dc.subject Tissue Array Analysis en
dc.subject Immunohistochemistry en
dc.subject Gene Expression Profiling en
dc.subject Signal Transduction en
dc.subject RNA Interference en
dc.subject Female en
dc.subject Practice Guidelines as Topic en
dc.subject MCF-7 Cells en
dc.subject Biomarkers, Tumor en
dc.title Multimodal assessment of estrogen receptor mRNA profiles to quantify estrogen pathway activity in breast tumors en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.clbc.2016.09.001 en
pubs.issue 2 en
pubs.begin-page 139 en
pubs.volume 17 en
dc.description.version VoR - Version of Record en
dc.rights.holder Copyright: The authors en
dc.identifier.pmid 27756582 en
pubs.end-page 153 en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 544146 en Medical and Health Sciences en Medical Sciences en Molecular Medicine en Oncology en School of Medicine en Obstetrics and Gynaecology en Science en Science Research en Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1938-0666 en
pubs.record-created-at-source-date 2017-10-09 en
pubs.dimensions-id 27756582 en

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