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FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells

Biswajyoti Sahu1, Marko Laakso, Päivi Pihlajamaa

  • 1Institute of Biomedicine and Research Programs Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki, Finland.

Cancer Research
|December 28, 2012
PubMed

Insights

Forkhead protein FoxA1 influences androgen receptor (AR) and glucocorticoid receptor (GR) binding sites, revealing cell-type specificity. GR significantly overlaps with AR targets, impacting prostate cancer pathways.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cancer Research

Background:

  • The forkhead protein FoxA1 is known as a pioneer factor.
  • FoxA1 depletion causes significant redistribution of androgen receptor (AR) and glucocorticoid receptor (GR) cistromes.

Purpose of the Study:

  • To investigate the novel function of FoxA1 in defining cell-type specificity for AR and GR binding.
  • To explore the interplay between AR and GR in prostate cancer, particularly the role of GR.

Main Methods:

  • ChIP-sequencing to map AR and GR binding sites.
  • Analysis of cis-element enrichment near binding sites.
  • Gene expression analysis to assess transcription programs.

Main Results:

  • FoxA1 dictates cell-type-specific AR binding in LNCaP-1F5 cells and GR binding in VCaP cells.
  • Distinct cis-element compositions are associated with AR and GR binding sites.
  • Significant overlap exists between AR and GR cistromes and transcription programs.
  • GR regulates AR-specific genes and can attenuate AR activity in the presence of androgen.

Conclusions:

  • FoxA1 plays a crucial role beyond pioneering, influencing AR and GR cistrome specificity.
  • GR's extensive overlap with AR targets suggests a significant role in prostate cancer, potentially in castration resistance.
  • Ligand-bound GR acts as a partial antiandrogen, modulating AR-dependent transcription.

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