Estrogen-related receptor γ modulates cell proliferation and estrogen signaling in breast cancer

Nobuhiro Ijichi1, Takashi Shigekawa, Kazuhiro Ikeda

  • 1Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.

Insights

Estrogen-related receptor gamma (ERRγ) is frequently expressed in breast cancer and promotes cell proliferation. Estrogen up-regulates ERRγ, suggesting ERRγ modulates estrogen signaling in hormone-dependent breast cancer.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Breast cancer is often hormone-dependent, influenced by estrogen and progesterone.
  • Estrogen-related receptors (ERRs) are structurally similar to estrogen receptors (ERs) and are implicated in breast cancer progression.
  • The specific role of ERRγ in breast cancer and its interaction with estrogen signaling requires further elucidation.

Purpose of the Study:

  • To investigate the expression of ERRγ in human invasive breast cancers.
  • To determine the relationship between ERRγ expression and clinicopathological characteristics.
  • To explore the functional role of ERRγ in estrogen signaling and breast cancer cell proliferation.

Main Methods:

  • Immunohistochemical analysis of ERRγ expression in 110 human invasive breast cancer samples.
  • In vitro studies using MCF-7 and 293T cells to assess ERRγ mRNA regulation by estrogen and its effect on cell proliferation and transcriptional activity.
  • Treatment with estrogen and ICI 182,780 to evaluate estrogen-dependent regulation of ERRγ.

Main Results:

  • Nuclear ERRγ immunoreactivity was detected in 79% of breast cancer cases and correlated with lymph node status.
  • Estrogen dose-dependently up-regulated ERRγ mRNA in MCF-7 cells, an effect blocked by ICI 182,780.
  • Overexpression of ERRγ increased MCF-7 cell proliferation and enhanced estrogen response element (ERE)-driven transcription, with or without ERα.

Conclusions:

  • ERRγ is frequently expressed in invasive breast cancer and may serve as a prognostic marker.
  • Estrogen signaling positively regulates ERRγ expression in breast cancer cells.
  • ERRγ functions as a modulator of estrogen signaling, promoting breast cancer cell proliferation and transcriptional activity.

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