Unraveling the regulatory connections between two controllers of breast cancer cell fate

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dc.citation.journalTitleNucleic Acids Research
dc.contributor.authorLee, Jinho
dc.contributor.authorTiwari, Abhinav
dc.contributor.authorShum, Victor
dc.contributor.authorMills, Gordon B.
dc.contributor.authorMancini, Michael A.
dc.contributor.authorIgoshin, Oleg A.
dc.contributor.authorBalázsi, Gábor
dc.date.accessioned2014-08-01T19:09:26Z
dc.date.available2014-08-01T19:09:26Z
dc.date.issued2014
dc.description.abstractEstrogen 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.identifier.citationLee, Jinho, Tiwari, Abhinav, Shum, Victor, et al.. "Unraveling the regulatory connections between two controllers of breast cancer cell fate." <i>Nucleic Acids Research,</i> (2014) Oxford University Press: http://dx.doi.org/10.1093/nar/gku360.
dc.identifier.doihttp://dx.doi.org/10.1093/nar/gku360
dc.identifier.urihttps://hdl.handle.net/1911/76330
dc.language.isoeng
dc.publisherOxford 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.titleUnraveling the regulatory connections between two controllers of breast cancer cell fate
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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