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TR3 orphan nuclear receptor mediates apoptosis through up-regulating E2F1 in human prostate cancer LNCaP cells

Xiaomin Mu1, Chawnshang Chang

  • 1George Whipple Laboratory for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, New York 14642, USA.

The Journal of Biological Chemistry
|August 30, 2003
PubMed

Insights

The study reveals that 12-O-tetradecanoylphorbol-13-acetate (TPA) triggers prostate cancer cell death by upregulating the TR3 orphan receptor (TR3) and apoptosis mediator E2F1. This pathway highlights a potential therapeutic target for prostate cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Early research indicated roles for TR3 orphan receptor (TR3) and E2F1 in prostate cancer apoptosis.
  • The precise relationship between TR3 and E2F1 in this context was not fully understood.

Purpose of the Study:

  • To elucidate the molecular pathway linking TR3 and E2F1 in TPA-induced apoptosis of LNCaP prostate cancer cells.
  • To investigate the regulatory mechanism of E2F1 expression by TR3.

Main Methods:

  • Utilized LNCaP prostate cancer cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA).
  • Employed antisense E2F1 and TR3 dominant-negative plasmid transfections.
  • Performed promoter reporter assays and electrophoretic mobility shift assays (EMSAs) to assess TR3 binding to the E2F1 promoter.

Main Results:

  • TPA induced apoptosis in LNCaP cells through increased expression of TR3 and E2F1.
  • TR3 mediated apoptosis, and E2F1 knockdown partially rescued this effect.
  • TR3 directly binds to a specific response element (TR3RE) in the E2F1 promoter, inducing its expression.

Conclusions:

  • A signaling cascade involving TPA → TR3 → E2F1 → apoptosis was identified in LNCaP cells.
  • TR3 acts as an upstream regulator of E2F1 in this apoptotic pathway.
  • Targeting this TPA-TR3-E2F1 pathway may offer strategies for controlling prostate cancer progression.

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