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Steroid 5alpha-reductase isozymes I and II in recurrent prostate cancer

Mark A Titus1, Christopher W Gregory, O Harris Ford

  • 1Department of Pathology and Laboratory Medicine, Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7295, USA. matitus@med.unc.edu

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|June 17, 2005
PubMed
Abstract

Insights

Recurrent prostate cancer shows increased steroid 5alpha-reductase type I (S5alphaRI) and decreased type II (S5alphaRII) activity. Dual inhibition of both isozymes may slow prostate cancer growth.

Area of Science:

  • Urology
  • Oncology
  • Biochemistry

Background:

  • Prostate cancer recurrence during androgen deprivation therapy (ADT) is common.
  • Circulating androgens are reduced in ADT, yet recurrent tumors maintain testosterone levels.
  • Dihydrotestosterone (DHT) levels are sufficient for androgen receptor activation in recurrent prostate cancer.

Purpose of the Study:

  • To characterize the expression and activity of steroid 5alpha-reductase isozymes I (S5alphaRI) and II (S5alphaRII) in prostate tissues.
  • To investigate the role of 5alpha-reductase activity in recurrent prostate cancer.

Main Methods:

  • Tissue microarrays of recurrent prostate cancer, benign prostate, and prostate cancer tissues.
  • Immunoblotting and immunohistochemistry using S5alphaRI and S5alphaRII antibodies.
  • Measurement of isozyme activities in tissue specimens.

Main Results:

  • Nuclear S5alphaRI expression was significantly higher than S5alphaRII in all tissue types.
  • Immunoblots confirmed higher S5alphaRI expression in recurrent prostate cancer; S5alphaRII was not detected.
  • S5alphaRI activity was 3.7-fold higher than S5alphaRII activity in recurrent prostate cancer.

Conclusions:

  • Recurrent prostate cancer exhibits a shift in expression and activity from S5alphaRII toward S5alphaRI.
  • Dual inhibition of S5alphaRI and S5alphaRII may reduce DHT biosynthesis.
  • Targeting both isozymes could prevent or delay the growth of recurrent prostate cancer.

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