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Journal of Endocrinological Investigation

, Volume 33, Issue 10, pp 745–750 | Cite as

Krüppel-like factor 4 mediates anti-proliferative effects of progesterone with G0/G1 arrest in human endometrial epithelial cells

  • Y. Shimizu
  • T. Takeuchi
  • S. Mita
  • T. Notsu
  • K. Mizuguchi
  • S. Kyo
Original Articles

Abstract

Activation of the progesterone receptor (PR) inhibits cell proliferation in various reproductive tissues. However, the molecular mechanisms underlying the regulation of cell proliferation by PR remain poorly understood. It is well established that Krüppel-like factor 4 (KLF4), a family of zinc finger-containing transcription factors, induces cell cycle arrest in epithelial cells. In this study, we investigated whether KLF4 served as a target of PR activation during cell proliferation using human endometrial epithelial cells. PR agonists, progesterone and dienogest, were found to produce a lasting increase in the expression of KLF4 mRNA, followed by a decrease in cyclin D1 mRNA, and inhibit cell proliferation with G0/G1 arrest. KLF4 knockdown using KLF4 small interferingRNA abrogated the inhibition of cell proliferation by PR agonists. In addition, forced expression of KLF4 inhibited cyclin D1 promoter transactivation. These results suggest that PR agonists induce KLF4 expression and then inhibit cyclin D1 expression, and consequently inhibit cell proliferation in human endometrial epithelial cells. In terms of human reproductive tissue, KLF4 may be a factor concerning cell cycle, directly responsive to PR activation.

Key-words

Cell proliferation dienogest endometrial epithelial cells Krüppel-like factor 4 progesterone 

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Copyright information

© Italian Society of Endocrinology (SIE) 2010

Authors and Affiliations

  • Y. Shimizu
    • 1
  • T. Takeuchi
    • 1
  • S. Mita
    • 1
  • T. Notsu
    • 1
  • K. Mizuguchi
    • 1
  • S. Kyo
    • 2
  1. 1.Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd.Gotemba, ShizuokaJapan
  2. 2.Department of Obstetrics and Gynecology, Graduate School of Medical ScienceKanazawa UniversityKanazawaJapan

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