Estrogen Receptor β: Switching to a New Partner and Escaping from Estrogen

Sci. Signal., 12 April 2011
Vol. 4, Issue 168, p. pe19
DOI: 10.1126/scisignal.2001991

Estrogen Receptor β: Switching to a New Partner and Escaping from Estrogen

  1. Yuet-Kin Leung1,2,3 and
  2. Shuk-Mei Ho1,2,3,*
  1. 1Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, University of Cincinnati Medical Center, Kettering Complex, Room 128, 3223 Eden Avenue, P.O. Box 670056, Cincinnati, OH 45267, USA.
  2. 2Center of Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA.
  3. 3Cincinnati Cancer Center, College of Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA.
  1. *Corresponding author. E-mail, shuk-mei.ho{at}uc.edu

Abstract

Estrogen receptor (ER) β, the “second” ER, plays a gatekeeper role by inhibiting cell proliferation, promoting apoptosis, and impeding the progression of prostate cancer. Ironically, its presumed ligand, 17β-estradiol, promotes cancer development in experimental models. The mechanisms underlying the interplay between estrogens and ERβ in prostate cancer remain largely unclear. Research on a previously unknown tethering partner of ERβ, Krüppel-like zinc finger transcription factor 5 (KLF5), and its downstream gene target (FOXO1) helps to unlock this puzzle. 17β-Estradiol is not required to maintain the tumor-suppressive function of ERβ in the prostate, a tissue with limited estrogen availability; moreover, the presence of 17β-estradiol abrogates ERβ- and KLF5-mediated signaling and promotes cellular proliferation. Future research into ERβ will likely involve this estrogen independency and the preference for binding nonclassical DNA elements through tethering. The development of ERβ-based therapies may lead to improved drug efficacy.

Citation:

Y.-K. Leung and S.-M. Ho, Estrogen Receptor β: Switching to a New Partner and Escaping from Estrogen. Sci. Signal. 4, pe19 (2011).

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