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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Function of nuclear sex hormone receptors in gene regulation

Shigeaki Kato1, Takashi Sato, Tomoyuki Watanabe

  • 1Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan. uskato@mail.ecc.u-tokyo.ac.jp

Cancer Chemotherapy and Pharmacology
|November 8, 2005
PubMed

Insights

Sex hormone receptors, like estrogen and androgen receptors, interact with signaling pathways and co-regulatory complexes. Novel cross-talk between estrogen and growth factor signaling, and dioxin receptor interaction, influence cancer development.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Reproductive organ tumor development, including breast and prostate cancer, is often driven by sex hormones.
  • Nuclear sex hormone receptors are ligand-inducible transcription factors crucial for gene expression.
  • These receptors interact with co-regulatory complexes involved in chromatin remodeling and histone modification.

Purpose of the Study:

  • To investigate the novel cross-talk between estrogen and growth factor signaling pathways.
  • To explore the interaction of the dioxin receptor (AhR) with the estrogen receptor (ER).
  • To model androgen-independent prostate cancer using a transgenic mouse expressing a human androgen receptor (AR) mutant.

Main Methods:

  • Investigated estrogen receptor (ER) association with nuclear complexes, including spliceosomes.
  • Examined the interaction of phosphorylated ER with MAP kinase.
  • Observed dioxin receptor (AhR) association with ER.
  • Generated a transgenic mouse line expressing a human AR mutant using the Cre-loxP system.

Main Results:

  • A novel cross-talk between estrogen and growth factor signaling was identified through ER and spliceosome complex interaction.
  • Dioxin receptor (AhR) association modulates ER transactivation function.
  • Transgenic mice expressing the human AR mutant developed prostate hyperplasia.
  • AR mutants exhibited hypersensitivity to antagonists and endogenous hormones.

Conclusions:

  • Estrogen-dependent breast cancer development may involve signaling pathways beyond direct estrogen action.
  • Androgen receptor (AR) mutant hypersensitivity could potentiate hormone-dependency in prostate cancer.
  • Understanding these complex signaling interactions is crucial for cancer therapy.

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