5alpha-Androstane-3alpha,17beta-diol activates pathway that resembles the epidermal growth factor responsive pathways in stimulating human prostate cancer LNCaP cell proliferation

Prostate Cancer Prostatic Dis. 2004;7(4):364-74. doi: 10.1038/sj.pcan.4500761.

Abstract

5alpha-Androstane-3alpha,17beta-diol (3alpha-diol) is considered to have no androgenic effects in androgen target organs unless it is oxidized to 5alpha-dihydrotestosterone (5alpha-DHT). We used microarray and bioinformatics to identify and compare 3alpha-diol and 5alpha-DHT responsive gene in human prostate LNCaP cells. Through a procedure called 'hypervariable determination', a similar set of 30 responsive genes involving signal transduction, transcription regulation, and cell proliferation were selected in 5alpha-DHT-, 3alpha-diol-, and epidermal growth factor (EGF)-treated samples. F-means cluster and networking procedures showed that the responsive pattern of these genes was more closely related between 3alpha-diol and EGF than between 5alpha-DHT and 3alpha-diol treatments. We conclude that 3alpha-diol is capable of stimulating prostate cell proliferation by eliciting EGF-like pathway in conjunction with androgen receptor pathway.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anabolic Agents / pharmacology*
  • Androstane-3,17-diol / pharmacology*
  • Cell Proliferation / drug effects
  • Computational Biology
  • Epidermal Growth Factor / pharmacology
  • Gene Expression Profiling
  • Humans
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / genetics
  • Signal Transduction*
  • Tumor Cells, Cultured

Substances

  • Anabolic Agents
  • Receptors, Androgen
  • Androstane-3,17-diol
  • Epidermal Growth Factor