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Breast Cancer Research and Treatment

, Volume 147, Issue 2, pp 265–281 | Cite as

High NR2F2 transcript level is associated with increased survival and its expression inhibits TGF-β-dependent epithelial-mesenchymal transition in breast cancer

  • Cheng Zhang
  • Yong Han
  • Hao Huang
  • Like Qu
  • Chengchao ShouEmail author
Preclinical study

Abstract

NR2F2, a member of nuclear receptor subfamily 2, was shown to be associated with cancer, but its role in breast malignancy remains unclear. In this study, we aimed to explore the function of NR2F2 in breast cancer. We browsed GEO and TCGA databases and used Kaplan–Meier survival analysis to explore the association between NR2F2 transcript level and patient survival in breast cancer. NR2F2 expression in breast cancer tissues was evaluated by immunohistochemistry staining. NR2F2-related functions and its role in Epithelial-Mesenchymal Transition (EMT) were predicted by Gene Set Enrichment Analysis (GSEA) and validated by in vitro assays with NR2F2 knockdown MDA-MB231 and MCF7 cells. We found high NR2F2 transcript level was correlated with favorable overall survival and distant metastasis-free survival. Positive rate of NR2F2 protein tended to be decreased with the progression of malignancy. Results of in vitro migration and invasion assays suggested NR2F2’s potential in inhibiting invasiveness. NR2F2 was predicted to be negatively linked with EMT and TGF-β-pathway related genes, which was supported by observation of EMT-like morphology and changes in EMT-markers E-cadherin and Slug. Additionally, we found TGF-β inhibited the expression of NR2F2. GSEA also predicted that NR2F2 could be inversely associated with chemoresistance, which was verified by results of in vitro growth inhibition assays using chemotherapeutic agents. Our results demonstrated high NR2F2 transcript level was associated with favorable clinical outcome, which might be due to NR2F2’s inhibitory effect on TGF-β-dependent EMT and its role in inhibiting chemoresistance.

Keywords

NR2F2 Breast cancer Metastasis EMT TGF-β 

Notes

Acknowledgments

We deeply appreciate Bin Dong for assistance in pathological evaluation. We thank Caiyun Liu, Li Min, and Lixin Wang for helpful suggestions on study design and experimental procedures. This study was supported by National Basic Research Program (Grant No. 2010CB529303, 2013CB910504) and the National Natural Science Foundation of China (Grant No. 81230046, 81172367).

Conflict of interest

We declare no potential competing financial interests. The experiments described in the manuscript comply with the current laws of the countries in which they were performed.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Cheng Zhang
    • 1
  • Yong Han
    • 1
  • Hao Huang
    • 1
  • Like Qu
    • 1
  • Chengchao Shou
    • 1
    Email author
  1. 1.Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular BiologyPeking University Cancer Hospital & InstituteBeijingChina

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