High expression of orphan nuclear receptor NR4A1 in a subset of ovarian tumors with worse outcome

Evan Delgado, Michelle M. Boisen, Robin Laskey, Rui Chen, Chi Song, Jad Sallit, Zachary A. Yochum, Courtney L. Andersen, Matthew J. Sikora, Jacob Wagner, Stephen Safe, Esther Elishaev, Adrian Lee, Robert P. Edwards, Paul Haluska, George Tseng, Mark Schurdak, Steffi Oesterreich

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Objective 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. Methods 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. Results 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. Conclusions 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.

Original languageEnglish (US)
Pages (from-to)348-356
Number of pages9
JournalGynecologic oncology
Volume141
Issue number2
DOIs
StatePublished - May 1 2016

Keywords

  • Nuclear receptors
  • Ovarian cancer
  • Therapeutic target

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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    Delgado, E., Boisen, M. M., Laskey, R., Chen, R., Song, C., Sallit, J., Yochum, Z. A., Andersen, C. L., Sikora, M. J., Wagner, J., Safe, S., Elishaev, E., Lee, A., Edwards, R. P., Haluska, P., Tseng, G., Schurdak, M., & Oesterreich, S. (2016). High expression of orphan nuclear receptor NR4A1 in a subset of ovarian tumors with worse outcome. Gynecologic oncology, 141(2), 348-356. https://doi.org/10.1016/j.ygyno.2016.02.030