Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer.
Bottom Line: By applying systems-level re-analysis of publicly available gene expression data, we uncovered a potential regulator of ESR1.Moreover, expression of NR2E3 was significantly associated with recurrence-free survival and a favourable response to tamoxifen treatment in women with ER-positive breast cancer.Our results provide mechanistic insights on the regulation of ESR1 by NR2E3 and the clinical relevance of NR2E3 in breast cancer.
Affiliation: Department of Systems Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.Show MeSH
Related in: MedlinePlus
Mentions: When a patient cohort of all ER-positive breast cancer [Institut Jules Bordet (IJB) cohort, n = 349; Loi et al, 2007, 2008] was dichotomized by expression levels of ESR1, it was no longer associated with RFS (Fig 7A), whereas expression of NR2E3 was still a significant predictor of recurrence in this cohort (Fig 7B). Since ESR1 is also the best-known predictive marker for adjuvant therapy with tamoxifen (Kanavos, 2006; Loi et al, 2007), we assessed clinical relevance of NR2E3 expression in patients with ER-positive breast cancer who received systemic tamoxifen treatment (subset of IJB cohort, n = 263). Unlike ESR1, which lacks predictive value in ER-positive patients, expression of NR2E3 was significantly associated with RFS of patients (Fig 7C and D). This association remained significant even when only patients with lymph node-negative breast cancer were considered for analysis (subset of IJB cohort, n = 114; Fig 7E and F), indicating that expression level of NR2E3 might be useful in predicting the response of ER-positive and node-negative patients to tamoxifen treatment.
Affiliation: Department of Systems Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.