Tumor progression in the LPB-Tag transgenic model of prostate cancer is altered by vitamin D receptor and serum testosterone status

J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):368-71. doi: 10.1016/j.jsbmb.2010.03.062. Epub 2010 Mar 27.


Previous studies have suggested that 1,25 dihydroxyvitamin D(3) (1,25(OH)2D3) induces cell cycle arrest and/or apoptosis in prostate cancer cells in vitro, suggesting that vitamin D may be a useful adjuvant therapy for prostate cancer and a chemopreventive agent. Most epidemiological data however shows a weak link between serum 25(OH)D3 and risk of prostate cancer. To explore this dichotomy we have compared tumor progression in the LPB-Tag model of prostate in VDR knock out (VDRKO) and wild type (VDRWT) mice. On the C57BL/6 background LPB-Tag tumors progress significantly more rapidly in the VDRKO mice. VDRKO tumors show significantly higher levels of cell proliferation than VDRWT tumors. In mice supplemented with testosterone to restore the serum levels to the normal range, these differences in tumor progression, and proliferation are abrogated, suggesting that there is considerable cross-talk between the androgen receptor (AR) and the vitamin D axis which is reflected in significant changes in steady state mRNA levels of the AR, PCNA, cdk2 survivin and IGFR1 and 2 genes. These alterations may explain the differences between the in vitro data and the epidemiological studies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Calcifediol / blood
  • Calcifediol / metabolism
  • Cyclin-Dependent Kinase 2 / metabolism
  • Disease Progression
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Proliferating Cell Nuclear Antigen / metabolism
  • Prostatic Neoplasms / epidemiology
  • Prostatic Neoplasms / metabolism*
  • Receptor, IGF Type 1 / metabolism
  • Receptors, Androgen / metabolism
  • Receptors, Calcitriol / metabolism*
  • Repressor Proteins / metabolism
  • Survivin
  • Testosterone / blood*


  • Anticarcinogenic Agents
  • Antineoplastic Agents
  • Birc5 protein, mouse
  • Inhibitor of Apoptosis Proteins
  • Proliferating Cell Nuclear Antigen
  • Receptors, Androgen
  • Receptors, Calcitriol
  • Repressor Proteins
  • Survivin
  • Testosterone
  • Receptor, IGF Type 1
  • Cdk2 protein, mouse
  • Cyclin-Dependent Kinase 2
  • Calcifediol