Activation of the glucocorticoid receptor is associated with poor prognosis in estrogen receptor-negative breast cancer

Deng Pan, Masha Kocherginsky, Suzanne D. Conzen

Research output: Contribution to journalArticle

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Abstract

Estrogen receptor-negative (ER -) breast cancers have limited treatment options and are associated with earlier relapses. Because glucocorticoid receptor (GR) signaling initiates antiapoptotic pathways in ER - breast cancer cells, we hypothesized that activation of these pathways might be associated with poor prognosis in ER -disease. Here we report findings from a genome-wide study of GR transcriptional targets in a premalignant ER -cell line model of early breast cancer (MCF10A-Myc) and in primary early-stage ER - human tumors. Chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq) coupled to time-course expression profiling led us to identify epithelial-to-mesenchymal transition (EMT) pathways as an important aspect associated with GR activation. We validated these findings by carrying out a meta-analysis of primary breast tumor gene expression from 1,378 early-stage breast cancer patients with long-term clinical follow-up, confirming that high levels of GR expression significantly correlated with shorter relapse-free survival in ER - patients who were treated or untreated with adjuvant chemotherapy. Notably, in ER + breast cancer patients, high levels of GR expression in tumors were significantly associated with better outcome relative to low levels of GR expression. Gene expression analysis revealed that ER - tumors expressing high GR levels exhibited differential activation of EMT, cell adhesion, and inflammation pathways. Our findings suggest a direct transcriptional role for GR in determining the outcome of poor-prognosis ER - breast cancers.

Original languageEnglish (US)
Pages (from-to)6360-6370
Number of pages11
JournalCancer research
Volume71
Issue number20
DOIs
StatePublished - Oct 15 2011

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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