American Association for Cancer Research
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Supplementary Figures 1-3 from Activation of the Glucocorticoid Receptor Is Associated with Poor Prognosis in Estrogen Receptor-Negative Breast Cancer

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journal contribution
posted on 2023-03-30, 20:48 authored by Deng Pan, Masha Kocherginsky, Suzanne D. Conzen

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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. Cancer Res; 71(20); 6360–70. ©2011 AACR.