title: High expression of orphan nuclear receptor NR4A1 in a subset of ovarian tumors with worse outcome.
abstract: Nuclear receptors (NRs) play a vital role in the development and progression of several cancers including breast and prostate. Using TCGA data, we sought to identify critical nuclear receptors in high grade serous ovarian cancers (HGSOC) and to confirm these findings using in vitro approaches.
  
  
  
  In silico analysis of TCGA data was performed to identify relevant NRs in HGSOC. Ovarian cancer cell lines were screened for NR expression and functional studies were performed to determine the significance of these NRs in ovarian cancers. NR expression was analyzed in ovarian cancer tissue samples using immunohistochemistry to identify correlations with histology and stage of disease.
  
  
  
  The NR4A family of NRs was identified as a potential driver of ovarian cancer pathogenesis. Overexpression of NR4A1 in particular correlated with worse progression free survival. Endogenous expression of NR4A1 in normal ovarian samples was relatively high compared to that of other tissue types, suggesting a unique role for this orphan receptor in the ovary. Expression of NR4A1 in HGSOC cell lines as well as in patient samples was variable. NR4A1 primarily localized to the nucleus in normal ovarian tissue while co-localization within the cytoplasm and nucleus was noted in ovarian cancer cell lines and patient tissues.
  
  
  
  NR4A1 is highly expressed in a subset of HGSOC samples from patients that have a worse progression free survival. Studies to target NR4A1 for therapeutic intervention should include HGSOC.
authors.affiliation: University of Pittsburgh Drug Discovery Institute, Pittsburgh, PA, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Delgado
authors.affiliation: Division of Gynecologic Oncology, Magee-Womens Hospital of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Electronic address: boockmeiermm@mail.magee.edu.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Boisen
authors.affiliation: Division of Gynecologic Oncology, Magee-Womens Hospital of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Laskey
authors.affiliation: Department of Biostatistics and Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Biostatistics and Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Chi
authors.initials: C
authors.lastname: Song
authors.affiliation: Ross University School of Medicine.
authors.forename: Jad
authors.initials: J
authors.lastname: Sallit
authors.affiliation: Department of Medicine, Division of Hematology Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Yochum
authors.affiliation: Department of Pharmacology and Chemical Biology, Womens Cancer Research Center, Magee-Womens Research Institute, and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA; Molecular Pharmacology Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Andersen
authors.affiliation: Department of Pharmacology and Chemical Biology, Womens Cancer Research Center, Magee-Womens Research Institute, and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sikora
authors.affiliation: University of Pittsburgh Drug Discovery Institute, Pittsburgh, PA, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Wagner
authors.affiliation: Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Safe
authors.affiliation: Department of Pathology, Magee-Womens Hospital of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Esther
authors.initials: E
authors.lastname: Elishaev
authors.affiliation: Department of Pharmacology and Chemical Biology, Womens Cancer Research Center, Magee-Womens Research Institute, and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Lee
authors.affiliation: Division of Gynecologic Oncology, Magee-Womens Hospital of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Edwards
authors.affiliation: Department of Oncology and Pharmacology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Haluska
authors.affiliation: Department of Biostatistics and Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: George
authors.initials: G
authors.lastname: Tseng
authors.affiliation: University of Pittsburgh Drug Discovery Institute, Pittsburgh, PA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Schurdak
authors.affiliation: Department of Pharmacology and Chemical Biology, Womens Cancer Research Center, Magee-Womens Research Institute, and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Steffi
authors.initials: S
authors.lastname: Oesterreich
mesh_terms: D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D005260:Female; D016678:Genome; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D012333:RNA, Messenger
keywords: Nuclear receptors; Ovarian cancer; Therapeutic target