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dc.contributor.authorLee, Jinho
Tiwari, Abhinav
Shum, Victor
Mills, Gordon B.
Mancini, Michael A.
Igoshin, Oleg A.
Balázsi, Gábor
dc.date.accessioned 2014-08-01T19:09:26Z
dc.date.available 2014-08-01T19:09:26Z
dc.date.issued 2014
dc.identifier.citation Lee, Jinho, Tiwari, Abhinav, Shum, Victor, et al.. "Unraveling the regulatory connections between two controllers of breast cancer cell fate." Nucleic Acids Research, (2014) Oxford University Press: http://dx.doi.org/10.1093/nar/gku360.
dc.identifier.urihttps://hdl.handle.net/1911/76330
dc.description.abstract Estrogen receptor alpha (ERα) expression is critical for breast cancer classification, high ERα expression being associated with better prognosis. ERα levels strongly correlate with that of GATA binding protein 3 (GATA3), a major regulator of ERα expression. However, the mechanistic details of ERα–GATA3 regulation remain incompletely understood. Here we combine mathematical modeling with perturbation experiments to unravel the nature of regulatory connections in the ERα–GATA3 network. Through cell population-average, single-cell and single-nucleus measurements, we show that the cross-regulation between ERα and GATA3 amounts to overall negative feedback. Further, mathematical modeling reveals that GATA3 positively regulates its own expression and that ERα autoregulation is most likely absent. Lastly, we show that the two cross-regulatory connections in the ERα–GATA3 negative feedback network decrease the noise in ERα or GATA3 expression. This may ensure robust cell fate maintenance in the face of intracellular and environmental fluctuations, contributing to tissue homeostasis in normal conditions, but also to the maintenance of pathogenic states during cancer progression.
dc.language.iso eng
dc.publisher Oxford University Press
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/
dc.title Unraveling the regulatory connections between two controllers of breast cancer cell fate
dc.type Journal article
dc.contributor.funder John S. Dunn Foundation
dc.contributor.funder National Institute of General Medical Sciences
dc.contributor.funder National Institutes of Health
dc.contributor.funder National Cancer Institute
dc.contributor.funder W.M. Keck Center for Interdisciplinary Bioscience Training
dc.contributor.funder Cancer Prevention and Research Institute of Texas
dc.contributor.funder Dan L. Duncan Cancer Center at Baylor College of Medicine
dc.citation.journalTitle Nucleic Acids Research
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1093/nar/gku360
dc.identifier.pmcid PMC4066784
dc.identifier.pmid 24792166
dc.identifier.grantID Collaborative Research Award (John S. Dunn Foundation )
dc.identifier.grantID 1R01GM106027-01 (National Institute of General Medical Sciences )
dc.identifier.grantID DP2OD00648104 (National Institutes of Health )
dc.identifier.grantID U54 CA112970 08 (National Cancer Institute )
dc.identifier.grantID R01-GM096189-01 (National Institute of General Medical Sciences )
dc.identifier.grantID Computational Cancer Biology Training Program fellowship (W.M. Keck Center for Interdisciplinary Bioscience Training)
dc.identifier.grantID RP101489 (Cancer Prevention and Research Institute of Texas )
dc.identifier.grantID HD007495 (National Institutes of Health )
dc.identifier.grantID DK56338 (National Institutes of Health )
dc.identifier.grantID CA125123 (National Institutes of Health)
dc.type.publication publisher version


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This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.