Androgen regulation of prostasin gene expression is mediated by sterol-regulatory element-binding proteins and SLUG

Mengqian Chen1, Li-Mei Chen, Karl X Chai

  • 1Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, Florida 32816-2364, USA.

The Prostate
|March 17, 2006
PubMed
Abstract

Insights

Dihydrotestosterone (DHT) regulates prostasin expression in prostate cancer cells by stimulating SREBP transcription factors and repressing SLUG. SLUG, upregulated by DHT and EGF, silences epithelial genes during cancer progression.

Area of Science:

  • Molecular biology
  • Cancer research
  • Prostate cancer epigenetics

Background:

  • Prostasin is downregulated in hormone-refractory prostate cancer (HRPC).
  • Mechanisms of androgen regulation of prostasin expression are not fully understood.

Purpose of the Study:

  • To investigate the role of androgens, specifically dihydrotestosterone (DHT), in regulating prostasin expression.
  • To elucidate the involvement of transcription factors SREBP, SNAIL, and SLUG in prostasin gene regulation.

Main Methods:

  • LNCaP and DU-145 cells were treated with DHT or EGF.
  • mRNA expression of prostasin and related transcription factors was analyzed using real-time PCR.
  • Prostasin promoter activity was assessed in HEK-293 cells co-transfected with transcription factor cDNAs.

Main Results:

  • DHT upregulated SLUG mRNA expression in LNCaP cells and marginally increased SREBP-1c, SREBP-2, and SNAIL.
  • SREBP-1c and SREBP-2 significantly stimulated prostasin promoter activity, while SNAIL and SLUG repressed it.
  • SLUG counteracted SREBP-2-mediated prostasin promoter activation; EGF upregulated SNAIL and SLUG in DU-145 cells.

Conclusions:

  • DHT regulates prostasin expression through SREBP stimulation and SLUG repression.
  • SLUG acts as a key mediator, upregulated by DHT and EGF, contributing to gene silencing in prostate cancer progression.

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