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Single-cell states in the estrogen response of breast cancer cell lines

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Casale, Francesco Paolo, Giurato, Giorgio, Nassa, Giovanni, Armond, Jonathan W., Oates, Chris J., Corá, Davide, Gamba, Andrea, Mukherjee, Sach, Weisz, Alessandro and Nicodemi, Mario (2014) Single-cell states in the estrogen response of breast cancer cell lines. PLoS ONE , 9 (2). Article number e88485. doi:10.1371/journal.pone.0088485

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Official URL: http://dx.doi.org/10.1371/journal.pone.0088485

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Abstract

Estrogen responsive breast cancer cell lines have been extensively studied to characterize transcriptional patterns in hormone-responsive tumors. Nevertheless, due to current technological limitations, genome-wide studies have typically been limited to population averaged data. Here we obtain, for the first time, a characterization at the single-cell level of the states and expression signatures of a hormone-starved MCF-7 cell system responding to estrogen. To do so, we employ a recently proposed model that allows for dissecting single-cell states from time-course microarray data. We show that within 32 hours following stimulation, MCF-7 cells traverse, most likely, six states, with a faster early response followed by a progressive deceleration. We also derive the genome-wide transcriptional profiles of such single-cell states and their functional characterization. Our results support a scenario where estrogen promotes cell cycle progression by controlling multiple, sequential regulatory steps, whose single-cell events are here identified.

Item Type: Journal Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science, Engineering and Medicine > Research Centres > Centre for Complexity Science
Faculty of Science, Engineering and Medicine > Science > Statistics
Library of Congress Subject Headings (LCSH): Breast -- Cancer -- Hormone therapy, Estrogen
Journal or Publication Title: PLoS ONE
Publisher: Public Library of Science
ISSN: 1932-6203
Official Date: 25 February 2014
Dates:
DateEvent
25 February 2014Published
7 January 2014Accepted
12 September 2013Submitted
Volume: 9
Number: 2
Number of Pages: 11
Article Number: Article number e88485
DOI: 10.1371/journal.pone.0088485
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
Funder: Associazione italiana per la ricerca sul cancro (AIRC), Italy. Ministero dell'istruzione, dell'università e della ricerca (MIUR)
Grant number: IG-13176 (AIRC), PRIN 2010LC747T 002 (Italy)

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