Metabolomics

, Volume 8, Issue 6, pp 1026–1036

Androgen receptor activation results in metabolite signatures of an aggressive prostate cancer phenotype: an NMR-based metabonomics study

  • Neil MacKinnon
  • Amjad P. Khan
  • Arul M. Chinnaiyan
  • Thekkelnaycke M. Rajendiran
  • Ayyalusamy Ramamoorthy
Original Article

DOI: 10.1007/s11306-012-0398-4

Cite this article as:
MacKinnon, N., Khan, A.P., Chinnaiyan, A.M. et al. Metabolomics (2012) 8: 1026. doi:10.1007/s11306-012-0398-4

Abstract

Metabolomic studies have proven to provide a unique perspective of the cellular dysfunction developing as a result of prostate cancer (PCa) onset and progression, facilitated primarily by mass spectrometry (MS) and nuclear magnetic resonance (NMR) techniques. PCa develops as an androgen-dependent disease with the expression of the androgen receptor (AR), where patient treatment typically involves androgen ablation therapy. In response, it is theorized that PCa transforms to an androgen-hypersensitive or androgen-independent state, where treatment options are severely reduced. Under the hypothesis that AR stimulation increases the aggressivity of pre-existing PCa, NMR spectroscopy was utilized in the delineation of the metabonomic response of an androgen-dependent PCa cell line (LnCAP) as a result of AR activation. Metabolite profiles were determined after 12, 24, and 48 h of exposure to methyltrienolone (R1881), an AR agonist. Principal components analysis revealed the relative myo-inositol and phosphocholine levels were severely altered after androgen treatment. Furthermore, univariate analysis revealed multiple metabolic perturbations in response to R1881 exposure, including amino acid, choline, the phosphocholine/glycerophosphocholine ratio, and UDP-coupled sugar metabolism, which are consistent with reported measurements between normal and PCa samples. These results suggest that androgen-sensitive PCa may transform to an aggressive phenotype upon AR activation.

Keywords

NMR Metabonomic Prostate cancer LnCAP Androgen R1881 

Supplementary material

11306_2012_398_MOESM1_ESM.pdf (345 kb)
Supplementary material 1 (PDF 344 kb)
11306_2012_398_MOESM2_ESM.xls (66 kb)
Supplementary material 2 (XLS 66 kb)

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Neil MacKinnon
    • 1
  • Amjad P. Khan
    • 2
  • Arul M. Chinnaiyan
    • 2
    • 3
  • Thekkelnaycke M. Rajendiran
    • 2
  • Ayyalusamy Ramamoorthy
    • 1
  1. 1.Biophysics and Department of ChemistryUniversity of MichiganAnn ArborUSA
  2. 2.Michigan Center for Translational Pathology, Department of PathologyUniversity of Michigan, Medical SchoolAnn ArborUSA
  3. 3.Department of UrologyComprehensive Cancer Center and Howard Hughes Medical Institute, University of Michigan, Medical SchoolAnn ArborUSA

Personalised recommendations