Interaction of nuclear receptor ligands with the Vitamin D signaling pathway in prostate cancer

J Steroid Biochem Mol Biol. 2004 Nov;92(4):307-15. doi: 10.1016/j.jsbmb.2004.10.006. Epub 2004 Dec 16.


A number of hormonal ligands and/or the nuclear receptors that mediate their actions have been targeted for prostate cancer therapy. Androgens, the ligands for the androgen receptor (AR), are critical for the growth of prostate cancer. Inhibition of androgen production has been the mainstay of treatment for advanced prostate cancer for decades. Other more recently tested targets include retinoid receptors (RAR and RXR), glucocorticoid receptors (GR), estrogen receptors (ER) and peroxisome proliferator-activated receptors (PPAR). Calcitriol, acting through the Vitamin D receptor (VDR), has many tumor suppressive activities in the prostate, including inhibition of proliferation, induction of apoptosis and/or differentiation, and reduction of cellular invasion. Because of these properties, calcitriol and its less hypercalcemic analogs are being evaluated as agents to prevent or treat prostate cancer. Androgens, retinoids, glucocorticoids, estrogens and agonists of PPAR directly or indirectly impact Vitamin D signaling pathways, and vice versa. In order to design the most effective strategies to use calcitriol to prevent or treat prostate cancer, the interactions of other nuclear receptors and their ligands with the Vitamin D signaling pathway need to be considered.

Publication types

  • Review

MeSH terms

  • Alitretinoin
  • Androgen Receptor Antagonists
  • Androgens / metabolism
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Calcitriol / analogs & derivatives
  • Calcitriol / physiology
  • Calcitriol / therapeutic use
  • Drug Interactions
  • Glucocorticoids / physiology
  • Glucocorticoids / therapeutic use
  • Histone Deacetylase Inhibitors
  • Hormones / metabolism*
  • Humans
  • Male
  • PPAR gamma / agonists
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / physiopathology
  • Proteasome Inhibitors
  • Receptors, Androgen / metabolism
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Retinoids / physiology
  • Retinoids / therapeutic use
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Tretinoin / metabolism
  • Tretinoin / physiology
  • Tretinoin / therapeutic use
  • Vitamin D / pharmacology
  • Vitamin D / physiology*
  • Vitamin D / therapeutic use


  • Androgen Receptor Antagonists
  • Androgens
  • Glucocorticoids
  • Histone Deacetylase Inhibitors
  • Hormones
  • PPAR gamma
  • Proteasome Inhibitors
  • Receptors, Androgen
  • Receptors, Cytoplasmic and Nuclear
  • Retinoids
  • Vitamin D
  • Alitretinoin
  • Tretinoin
  • Calcitriol