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Androgen stimulates transcription and replication of xenotropic murine leukemia virus-related virus

Beihua Dong1, Robert H Silverman

  • 1Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.

Journal of Virology
|November 13, 2009
PubMed

Insights

Dihydrotestosterone (DHT) stimulates the transcription and replication of xenotropic murine leukemia virus-related virus (XMRV). This suggests that XMRV may exploit androgen signaling pathways in prostate cancer cells.

Area of Science:

  • Virology
  • Oncology
  • Molecular Biology

Background:

  • Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus found in some prostate cancer patients.
  • Androgens are known to stimulate prostate tumor growth and influence some retroviral activity.

Purpose of the Study:

  • To investigate the impact of dihydrotestosterone (DHT) on XMRV transcription and replication.
  • To determine if androgen signaling pathways affect XMRV activity.

Main Methods:

  • Assessed XMRV U3 region transcription in cells with functional androgen receptors.
  • Utilized mutations in the glucocorticoid response element (GRE) of XMRV.
  • Measured XMRV replication levels.
  • Examined the effect of androgen inhibitors (casodex, flutamide) on viral growth.

Main Results:

  • DHT increased XMRV transcription up to 2-fold in cells with functional androgen receptors.
  • Mutations in the XMRV GRE impaired basal transcription and androgen responsiveness.
  • DHT stimulated XMRV replication by 3-fold.
  • Androgen inhibitors suppressed XMRV growth by up to 3-fold.

Conclusions:

  • Androgens, specifically DHT, significantly enhance XMRV transcription and replication.
  • The XMRV long terminal repeat (LTR) may mediate androgen responsiveness.
  • XMRV integration into host DNA could potentially lead to androgen stimulation of cellular genes.

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