Finasteride upregulates expression of androgen receptor in hyperplastic prostate and LNCaP cells: implications for chemoprevention of prostate cancer

Prostate. 2011 Jul;71(10):1115-21. doi: 10.1002/pros.21325. Epub 2011 Jan 12.

Abstract

Background: Although finasteride is recognized for its role as a chemopreventive agent for prostate cancer, higher grades of malignancy have been reported. It is questioned whether blocking of testosterone conversion to dihydrotestosterone (DHT) by finasteride in prostate tissue will change expression of androgen receptor (AR). Therefore, this study evaluated the effects of finasteride on AR expression in prostate tissue and in the LNCaP cell line.

Methods: Between January and December 2006, we retrospectively selected and evaluated 47 cases of benign prostatic hyperplasia treated with variable duration of finasteride (5 mg QD) before transurethral resection of the prostate. AR expression in prostate tissue was semiquantified by immunostaining and compared with duration of finasteride treatment. An androgen-dependent prostate cancer cell line (LNCaP) was cultured in charcoal/dextran-treated FBS with DHT or testosterone, and treated with finasteride for 1-3 weeks. Samples of total RNA were collected to analyze expression of AR by real-time quantitative reverse transcription polymerase chain reaction.

Results: Immunohistochemical study revealed significant upregulation of ARs by finasteride treatment for 30-180 days. In cell line study, quantitative real-time reverse transcription polymerase chain reaction revealed significant upregulation of ARs treated by finasteride.

Conclusions: In our study, finasteride influenced AR expression in benign prostate tissue and prostate cancer cell. Before we can use finasteride in chemoprevention with confidence, we still need to clarify the influence of finasteride in ARs and its regulation pathway.

MeSH terms

  • 5-alpha Reductase Inhibitors / pharmacology*
  • 5-alpha Reductase Inhibitors / therapeutic use
  • Aged
  • Androgens / pharmacology
  • Cells, Cultured
  • Dihydrotestosterone / pharmacology
  • Finasteride / pharmacology*
  • Finasteride / therapeutic use
  • Humans
  • Immunohistochemistry
  • Male
  • Prostate / drug effects*
  • Prostate / metabolism
  • Prostatic Hyperplasia / drug therapy
  • Prostatic Hyperplasia / genetics
  • Prostatic Hyperplasia / metabolism*
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Testosterone / pharmacology
  • Up-Regulation / drug effects*

Substances

  • 5-alpha Reductase Inhibitors
  • Androgens
  • Receptors, Androgen
  • Dihydrotestosterone
  • Testosterone
  • Finasteride