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Kruppel-like factor 4 is a novel mediator of selenium in growth inhibition

Shuang Liu1, Haitao Zhang, Liyu Zhu

  • 1Department of Structural & Cellular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA.

Molecular Cancer Research : MCR
|March 4, 2008
PubMed

Insights

Selenium supplementation inhibits prostate cancer growth by up-regulating Krüppel-like factor 4 (KLF4). This transcription factor is crucial for selenium

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Nutritional Science

Background:

  • Selenium supplementation trials show a 50% reduction in prostate cancer incidence.
  • Selenium inhibits prostate cancer cell growth in vitro through various mechanisms.

Purpose of the Study:

  • To investigate the role of Krüppel-like factor 4 (KLF4) as a target of selenium in prostate cancer.
  • To elucidate the molecular mechanisms underlying selenium's anti-cancer effects.

Main Methods:

  • Selenium treatment of human prostate cancer cell lines (LNCaP and PC-3).
  • Analysis of KLF4 expression and DNA-binding activity.
  • KLF4 knockdown and overexpression studies.
  • Assessment of DNA synthesis, apoptosis, and target gene expression (cyclin D1, p21/WAF1, p27/Kip1).

Main Results:

  • Selenium up-regulates KLF4 expression and enhances its DNA-binding activity in prostate cancer cells.
  • Increased KLF4 expression is primarily due to enhanced transcription.
  • KLF4 knockdown diminishes selenium's effects on DNA synthesis inhibition and apoptosis induction.
  • KLF4 overexpression induces apoptosis and potentiates selenium's anti-cancer activities.

Conclusions:

  • Krüppel-like factor 4 (KLF4) is a key mediator of selenium's growth-inhibitory effects in prostate cancer cells.
  • Selenium's anti-cancer properties are significantly influenced by its regulation of KLF4.

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