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

PLoS One. 2014 Feb 25;9(2):e88485. doi: 10.1371/journal.pone.0088485. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Estrogens / genetics*
  • Estrogens / metabolism*
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MCF-7 Cells
  • Transcriptome / genetics

Substances

  • Estrogens

Grants and funding

The authors acknowledge funding for this work from the Italian Association for Cancer Research (http://www.airc.it/- Grant IG-13176) and the PRIN of the Italian Ministry for Education, University and Research (http://prin.miur.it/- Grant PRIN 2010LC747T 002) and a “Mario e Valeria Rindi” postdoctoral fellowship to GN from the Italian Foundation for Cancer Research (http://www.fondazionefirc.it/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.