title: Expression and functional pathway analysis of nuclear receptor NR2F2 in ovarian cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: Departments of Obstetrics and Gynecology, The Dan L Duncan Cancer Center, Baylor College of Medicine, The Methodist Hospital, Houston, Texas 77030, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Hawkins
authors.forename: Holli A
authors.initials: HA
authors.lastname: Loomans
authors.forename: Ying-Wooi
authors.initials: YW
authors.lastname: Wan
authors.forename: Triparna
authors.initials: T
authors.lastname: Ghosh-Choudhury
authors.forename: Donna
authors.initials: D
authors.lastname: Coffey
authors.forename: Weimin
authors.initials: W
authors.lastname: Xiao
authors.forename: Zhandong
authors.initials: Z
authors.lastname: Liu
authors.forename: Haleh
authors.initials: H
authors.lastname: Sangi-Haghpeykar
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Anderson
mesh_terms: D017209:Apoptosis; D051837:COUP Transcription Factor II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D010053:Ovary / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D010865:Pilot Projects; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis
chemical_list: D051837:COUP Transcription Factor II; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C095569:NR2F2 protein, human