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ELF3 is a repressor of androgen receptor action in prostate cancer cells.

Publication ,  Journal Article
Shatnawi, A; Norris, JD; Chaveroux, C; Jasper, JS; Sherk, AB; McDonnell, DP; Giguère, V
Published in: Oncogene
February 13, 2014

The androgen receptor (AR) has a critical role in the development and progression of prostate cancer (PC) and is a major therapeutic target in this disease. The transcriptional activity of AR is modulated by the coregulators with which it interacts, and consequently deregulation of cofactor expression and/or activity impacts the expression of genes whose products can have a role in PC pathogenesis. Here we report that E74-like factor 3 (ELF3), a member of the ETS family of transcription factors, is a repressor of AR transcriptional activity. Exogenous expression of ELF3 represses AR transcriptional activity when assessed using reporter-based transfection assays or when evaluated on endogenous AR target genes. Conversely, ELF3 knock down increases the AR transcriptional activity. Biochemical dissection of this activity indicates that it results from the physical interaction between ELF3 and AR and that this interaction inhibits the recruitment of AR to specific androgen response elements within target gene promoters. Significantly, we observed that depletion of ELF3 expression in LNCaP cells promotes cell migration, whereas increased ELF3 expression severely inhibits tumor growth in vitro and in a mouse xenograft model. Taken together, these results suggest that modulation of ELF3 expression and/or AR/ELF3 interaction may have utility in the treatment of PC.

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Published In

Oncogene

DOI

EISSN

1476-5594

Publication Date

February 13, 2014

Volume

33

Issue

7

Start / End Page

862 / 871

Location

England

Related Subject Headings

  • Tumor Burden
  • Transcription, Genetic
  • Transcription Factors
  • Response Elements
  • Repressor Proteins
  • Receptors, Androgen
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins
  • Protein Interaction Domains and Motifs
  • Protein Binding
 

Citation

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Shatnawi, A., Norris, J. D., Chaveroux, C., Jasper, J. S., Sherk, A. B., McDonnell, D. P., & Giguère, V. (2014). ELF3 is a repressor of androgen receptor action in prostate cancer cells. Oncogene, 33(7), 862–871. https://doi.org/10.1038/onc.2013.15
Shatnawi, A., J. D. Norris, C. Chaveroux, J. S. Jasper, A. B. Sherk, D. P. McDonnell, and V. Giguère. “ELF3 is a repressor of androgen receptor action in prostate cancer cells.Oncogene 33, no. 7 (February 13, 2014): 862–71. https://doi.org/10.1038/onc.2013.15.
Shatnawi A, Norris JD, Chaveroux C, Jasper JS, Sherk AB, McDonnell DP, et al. ELF3 is a repressor of androgen receptor action in prostate cancer cells. Oncogene. 2014 Feb 13;33(7):862–71.
Shatnawi, A., et al. “ELF3 is a repressor of androgen receptor action in prostate cancer cells.Oncogene, vol. 33, no. 7, Feb. 2014, pp. 862–71. Pubmed, doi:10.1038/onc.2013.15.
Shatnawi A, Norris JD, Chaveroux C, Jasper JS, Sherk AB, McDonnell DP, Giguère V. ELF3 is a repressor of androgen receptor action in prostate cancer cells. Oncogene. 2014 Feb 13;33(7):862–871.

Published In

Oncogene

DOI

EISSN

1476-5594

Publication Date

February 13, 2014

Volume

33

Issue

7

Start / End Page

862 / 871

Location

England

Related Subject Headings

  • Tumor Burden
  • Transcription, Genetic
  • Transcription Factors
  • Response Elements
  • Repressor Proteins
  • Receptors, Androgen
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins
  • Protein Interaction Domains and Motifs
  • Protein Binding