1. Expression and functional pathway analysis of nuclear receptor NR2F2 in ovarian cancer.
- Author
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Hawkins SM, Loomans HA, Wan YW, Ghosh-Choudhury T, Coffey D, Xiao W, Liu Z, Sangi-Haghpeykar H, and Anderson ML
- Subjects
- Apoptosis, COUP Transcription Factor II antagonists & inhibitors, COUP Transcription Factor II genetics, Cell Line, Tumor, Cell Proliferation, Epithelial Cells metabolism, Epithelial Cells pathology, Female, Gene Expression Profiling, Humans, Neoplasm Proteins antagonists & inhibitors, Neoplasm Proteins genetics, Ovarian Neoplasms pathology, Ovarian Neoplasms surgery, Ovary pathology, Ovary surgery, Pilot Projects, RNA Interference, RNA, Messenger metabolism, RNA, Small Interfering, Recombinant Proteins antagonists & inhibitors, Recombinant Proteins metabolism, Stromal Cells metabolism, Stromal Cells pathology, Survival Analysis, COUP Transcription Factor II metabolism, Gene Expression Regulation, Neoplastic, Neoplasm Proteins metabolism, Ovarian Neoplasms metabolism, Ovary metabolism, Signal Transduction
- Abstract
Context: Recent evidence implicates the orphan nuclear receptor, nuclear receptor subfamily 2, group F, member 2 (NR2F2; chicken ovalbumin upstream promoter-transcription factor II) as both a master regulator of angiogenesis and an oncogene in prostate and other human cancers., Objective: The objective of the study was to determine whether NR2F2 plays a role in ovarian cancer and dissect its potential mechanisms of action., Design, Setting, and Patients: We examined NR2F2 expression in healthy ovary and ovarian cancers using quantitative PCR and immunohistochemistry. NR2F2 expression was targeted in established ovarian cancer cell lines to assess the impact of dysregulated NR2F2 expression in the epithelial compartment of ovarian cancers., Results: Our results indicate that NR2F2 is robustly expressed in the stroma of healthy ovary with little or no expression in epithelia lining the ovarian surface, clefts, or crypts. This pattern of NR2F2 expression was markedly disrupted in ovarian cancers, in which decreased levels of stromal expression and ectopic epithelial expression were frequently observed. Ovarian cancers with the most disrupted patterns of NR2F2 were associated with significantly shorter disease-free interval by Kaplan-Meier analysis. Targeting NR2F2 expression in established ovarian cancer cell lines enhanced apoptosis and increased proliferation. In addition, we found that NR2F2 regulates the expression of NEK2, RAI14, and multiple other genes involved in the cell cycle, suggesting potential pathways by which dysregulated expression of NR2F2 impacts ovarian cancer., Conclusions: These results uncover novel roles for NR2F2 in ovarian cancer and point to a unique scenario in which a single nuclear receptor plays potentially distinct roles in the stromal and epithelial compartments of the same tissue.
- Published
- 2013
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