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Estrogen-related receptor-γ regulates estrogen receptor-α responsiveness in uterine endometrial cancer

Takuro Yamamoto1, Taisuke Mori, Morio Sawada

  • 1Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society
|October 12, 2012
PubMed
Abstract

Insights

Estrogen-related receptor gamma (ERRγ) expression impacts uterine endometrial cancer cell growth differently based on estrogen receptor alpha (ERα) status. ERRγ/ERα status may predict prognosis and guide treatment for endometrial cancer.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Estrogen-related receptors (ERRs) are orphan nuclear receptors involved in cancer cell growth.
  • The role of ERRγ in uterine endometrial cancer and its interaction with the estrogen receptor (ER)-mediated pathway are not well understood.

Purpose of the Study:

  • To measure ERRγ expression in human endometrial cancer.
  • To investigate the association between ERRγ and the ER-mediated pathway.
  • To determine the functional role of ERRγ in endometrial cancer cell lines.

Main Methods:

  • Cell proliferation, luciferase, and quantitative PCR assays were conducted in ERα-positive and ERα-negative endometrial cancer cell lines.
  • Immunohistochemical analysis was used to assess ERRγ and ERα expression in tumor tissues.
  • The effects of a selective ERRγ agonist (DY131) on cell growth were evaluated.

Main Results:

  • ERRγ differentially regulated estrogen-induced transcriptional activity and cell growth in ERα-positive versus ERα-negative cells.
  • A selective ERRγ agonist inhibited growth in ERα-positive cells but promoted it in ERα-negative cells.
  • ERRγ nuclear expression was observed in endometrial cancer tissues, with ERRγ-positive/ERα-negative status correlating with a potentially poor prognosis.

Conclusions:

  • The interplay between ERRγ and ERα status may serve as a predictive marker for uterine endometrial cancer treatment.
  • Further research into ligands for ERRγ is warranted to explore therapeutic strategies.

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